List III

Topic III/ 1 Neurological disorders caused by viral infections

Definition
Invasion of the nervous system by virus may be as part of a generalized viral infection in the whole body. On the
other hand, CNS signs may be unproportionally severe compared with the general signs.
Pathogenesesis
Viruses enter via resp. tract, GI.tract, genitourinary tract or through skin. Infection depends on:
Previous exposure

Patients IgA neutralize

Viral entry
No previous exposure

VIREMIA
Along peripheral nerves

Massive
Infection

Overcomes monocyte and

reticuloendothelial defence
systems

Invades CNS via capillaries

and nerves

Invades CNS

Classification
Meninges

Meningitis

Parenchyma

Encephalitis
Rapid progressive
Slowly progressive
Reactive
Reye syndrome
Cerebellitis

Myelitis

Motor neurons of
cranial and spinal
nerves

Poliomyelitis

Dorsal root ganglia

Radiculitis

Peripheral nerves

Infection
Immune reaction

Meningitis
Acute aseptic viral meningitis
Viral agent
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

Comment

Enterovirus
Mumps
Herpes simplex virus (type 2)
Arbovirus
EBV
CMV
Adenovirus
Influenza A, B
Measles, rubella, VZV, parainfluenza.
Picornavirus (polio)
HIV
Lymphocytic choriomeningitis virus (LCMV)

Fecal-oral in children. Exanthema and other signs.

Winter virus. Commonest worldwide. Often males.
Sexually active adults.
Summer-virus

Spread from rodent droppings. Any age.

Symptoms
Prodromal phase

Meningeal phase

Fever

Headache

Malaise

Photophobia

Sore throat

Drowsiness

Recovery 7-14 days

Signs

Mild meningism: can include retrobulbar headache, meningeal irritation (neck stiffness, positive
Kernig`s sign and Brudzinsky), parotitis, diarrhea or myalgia,
Signs of parenchyma involvement: impaired level of consciousness. Seizures, confusion, coma, focal
neurological signs.

Clinical symptoms depends on the particular virus and the cells on the nervous system which show a specific
susceptibility.
Diagnosis
1. CSF (if taken early, often recoverable virus)
o Only contraindication of LP is if ICP and there is space-occupying lesion.
o Lymphocytes or monocytes in CSF. protein, normal glucose.
2. PCR detection of DNA/RNA is diagnostic.
3. Virus culture from throat swabs or stool.
4. Serology: measure antigen for a specific virus
o (CSF organism specific Ig)/(CSF total Ig)
o (serum organism specific)/(Ig serum total Ig) - if the ratio is >1.5 it means more virus specific
Ig in the CSF than in blood
DD Though viral meningitis is considered mild and is self-limited, don`t confuse with more severe meningitis
caused by a variety of non-viral agents (eg TBC, sarcoidosis, carcinomatous)
Prognosis and treatment is excellent and treatment symptomatic. If herpes simplex meningitis w/
encephalitic component, give IV acyclovir.

Encephalitis
Types
Direct
Indirect
Toxic
encephalopathy

Acute viral encephalitis

Meningoencephalitis
Allergic or postinfectious encephalomyelitis
Develops during the course of a viral illness in which inflammation is not a pathological
feature Reye syndrome.

Acute viral encephalitis

This viral infection causes neuronal and glial damage with associated inflammation and edema. It
occurs worldwide, most often in tropics.
Encephalitis following childhood infections measles, varicella, rubella, is presumed to be
postinfectious and not due to viral invasion.
Causative agents
World-wide
1. Mumps
2. Herpes simplex
3. Varicella zoster
4. Epstein-Barr
5. Arboviruses

Rare forms in specific areas

1. Western equine vector mosquito in USA
2. West Nile vector mosquito Africa/India
3. Russion spring/summer vector tick eastern Europa

Signs and symptoms

General (eg. pyrexia, myalgia) and specific to causative virus (eg infectious mononucleosis in EBV)
In general, the illness lasts for some weeks.
Cerebrum - coma, confusion, dysphasia (only speech impairment),
hemiparesis, involuntary movements and epilepsy
Midbrain - oculomotor palsy and autonomic disturbance
Cerebellum - dysarthria and ataxia
Brain stem - cranial nerve palsies, nystagmus and tetraparesis
Spinal cord - autonomic, motor and sensory dysfunction
Prognosis
Uncertain, and depends on the causal virus as do neurological sequelae.

Rapidly progressive
Rabies
Pathogenesis
Rhabdovirus (Sylvian-wild or Urban-domestic type), infects through bites from an infected mammal. Incubation
for 9 - 90 days. ACh-nerves are slowing down to paralyze the affected body parts. The closer the bite is to head,
the faster the migration to brain!
Symptoms
Prodrome
Headache
Malaise
Abnormal
behaviour

Acute encephalitis
Agitation
Hyperactivity
Confusion
Seizures

Classic brainstem encephalitis

Cranial nerve dysfunction
(drooping)
Hydrophobia (foam)
Photophobia

Death
Due to respiratory
paralysis

Treatment
Clean wound!
Animal or human vaccine (live, attenuated)
Injection with antibodies (passive method, IgG) partly in the wound, partly IM.
Look out for animals which normally stays away if they are approaching without fear..!
Slowly progressive
The following diseases are chronic by nature:
Subacute sclerosing panencepahlitis (SSPE)
Pathogenesis

This is caused by measles. Children are mostly affected.

Incomplete virus that cannot bud off from the cells replicate in oligodendroglia + neurons (inclusion
bodies) later spread from cell to cell chronic encephalitis.
Involves both grey and white matter.

Symptoms
Stage 1
Behavioral problem
Declining school
performance
Progression demenMa

Stage 2
Chorioretinitis
Myoclonic jerks
Seizures and ataxia
Dystonia

Stage 3
Lapses into rigid comatose state

NB! Accompanying symptoms of infection, i.e.pyrexia, leukocytosis, are absent.

The condition may persist for more than 10 years.
Diagnosis
CSF
Blood
EEG

75% - measles IgG antibodies

Elevated serum measles antibodies
Periodic high voltage slow wave complexes on a low voltage background

Treatment
No effective treatment, but since introduction of vaccine the incidence of SSPE has been low

Progressive rubella panencephalitis (normal EEG)

Similar to SSPE, EEG doesnt show periodic complexes.
Acute dissemniated encephalopmyelitis (ADEM)
Perivascular demyelination developing after viral infection (influenza, rubella, VZV)
There is fever headache, nausea, meningism, focal neurological signs, myoclonus, optic neuritis.
Diagnosis
CSF
protein,
lymphocytes
EEG - generalized asynchronous slow activity
Treatment
Steroids
Progressive multifocal leukoencephalopathy (PML)
Pathogenesis
A demyelination disorder in association with systemic illnesses where the cellular immunity is impaired (eg.
AIDS, lymphoma, sarcoidosis, SLE. Caused by reactivation of previous papovavirus (SV40 or JC virus)
Symptoms
Initial visual impairment and mental impairment. Later motor weakness develops.
Diagnosis
CT & MRI are diagnostic lesions are seen in the periventricular position
EEG: slow waves
Therapy - no effective therapy

Tropical spastic paraparesis (HTLV)

Clinical presentation: spastic paraparesis / paraplegia, hyperactive tendon reflexes, clonus, extensor plantar
responses. Paresthesia, pain in the legs. Frontal release signs and cranial abnormalities are rarely seen.
Causative agent is HTLV-I acquired through blood transfusion, sex, IV drug use, mother to fetus.
No definitive treatment (i.e. prednisolone, zidovudinve)
The demyelination of the different tract of the spinal cord, are demonstrated by evoked potentials study.
Peripheral nerve involvement is characterized by slowed conduction velocities, increased distal latencies, slow F
wave.
Myelitis and radiculitis
Many viruses can cause this inflammation, typically poliovirus, EBV, mumps.
Treatment is generally supportive.
Paralytic polio
Agent: picorna virus (enterovirus)
Pathogenesis: infection of the anterior horn cells, motor nuclei of the brainstem
Clinical: Prodromal symptoms: fever, headache, myalgia, pharyngitis, nausea, vomiting,
Meningeal without paralysis
Paralysis: lower motor neuron
brain stem motor neuron (pseudobulbar palsy or bulbar palsy)
No sensory loss
Loss of superficial reflexes
vaccine: live attenuated (Sabin)
5

Reye syndrome
General
Rare encephalopathy almost only in children. It occurs when aspirin is used to treat Influenza A, B or varicellazoster infections.
Pathogenesis
BRAIN

Brain EDEMA
Brain shift

VIRUS
+ salicylates
+ genetic
disposition (enzyme
deficiency)

Mitochondrial
damage
Hypoglycemia
LIVER

Fails to detoxify
substances which
disturb
neurotransmission

BRAIN DAMAGE

Neuronal and glial cells are swollen, liver, heart and kidneys show fatty infiltration.
Clinical features
Prodromal symptoms
of viral infection

latent period
variable duration

Diagnosis
1. Blood test
ASAT and ALAT

serum ammonia

2. CT/MRI shows diffuse cerebral edema

Hypoglycemia (in infants)

Prothrombin Mme

Prognosis
Early diagnosis and supportive treatment has reduced mortality from 80% to 30%.

Rapid onset
Vomiting
Delirium
Convulsions
Coma
Hepatomegaly in 50%
Usually no focal
neurological signs

serum faRy acids

Aminoaciduria

Topic III/2 Neurological disorders caused by Herpes virus

General
HSV 1 and 2 commonly cause disease in humans. Varicella (chickenpox) and varicella zoster (shingles) are
different clinical manifestations of the same virus, namely VZV or HHV3.
Herpes viruses
HHV1
HHV2
HHV3

Oral and labial rashes as well as encephalitis

Genital and neonatal infection as well as meningitis
Acute encephalitis
Postinfectious encephalomyelitis
Viral meningitis
Postinfectious polyneuropathy (Guillain-Barr
syndrome)
Myelitis
Ramsay Hunt syndrome

Symptoms and signs

HHV1 and HHV2
Occuring in all seasons, at all ages and all over the world. Most common cause of severe encephalitis.
General symptoms at onset (meningism): headache and fever, evolution over
days to seizures and impaired level of consciousness.
Inferior frontal and temporal lobes are selectively involved producing
parynchemal disturbance and symptoms accordingly:

Diagnosis

Olfactory and gustatory hallucinations

Behavioral disturbance
Epileptic seizures: Grand mal or complex partial seizures
Dysphasia (dominant hemispheres) and hemiparesis
Cerebral edema may result in tentorial herniation
Wernicke involvement jargon aphasia

CT
temporal hypodensity due to haemorrhagic infarcMon which is a typical sign (pracMce note!)
MRI
temporal lobe involvement (specific to HSV) T1 hyperdense
EEG
slow wave changes, periodic complexes on the temporofrontal region , which is specific to HSV
PCR
early diagnosis detection of HSV DNA in CSF
CSF
5-500 lymphocytes. Mildly eleveated protein, normal glucose.
Treatment
Acyclovir reduces mortality from 79 to 20%. Non-toxic drug, so give on suspicion. No reason to wait!
Prognosis
80% mortality with no treatment, 30% if treated.
Amnesia is a common sequel of HSV encephalitis
HHV3
First chickenpox no symptoms unMl immunocomprimised and > age 50 reacMvaMon shingles.
Symptoms
Vesicular rash w/
Vesicles crust and skin is irregular with depigmentation and scarring.
burning and painful
1-3 weeks
Myelitis/encephalitis in immunocomprimised.
sensation on
Trigeminal involvement herpes zoster ophthalmicus
dermatome
Geniculate ggl. vesicles within ext.ac.meatus with ipsilat. deafness
distribution
and facial weakness (Ramsay Hunt syndrome)
Diagnosis and treatment
Based on clinical symptoms. Treatment is symptomatic if not severe disease, but when immunodeficient patient
or ophthalmic vesicles acyclovir.
7

Topic III/ 3 Prion-diseases, slow virus infections

Prion diseases
Etiology/pathogenesis
The word prion is a compound word derived from the initial letters of the words proteinaceous and infectious,
with -on added by analogy to the word virion. Before 1982, when the term prion was introduced to the scientific
world, the degenerative CNS diseases we at present know are caused by the structural alteration in the
c
endogenous PrP protein, were thought to be caused by slow virus infections. Mechanism of prion infection and
propagation remains mysterious.
c
PrP c for cellular protein (normal endogenous protein found in many tissues)
sc
PrP sc for scrapie (abnormal protein which accumulates and causes neuronal damage)
sc

PrP conversion amyloid fold, in

which the protein polymerises
aggregate consisting of tightly packed
sc
beta sheets. Inoculation of PrP in cell
membrane modifies normal cell
membrane protein which acts as a
template for further conversion to
abnormal protein. Extremely stable
structure makes the protein virtually
impossible to dispose with chemical or
physical methods.

The Prion theory

The Prion theory was introduced in 1982 by Stanley B. Prusiner. The idea of a disease causing agent consisting
of protein only came from noticing that the diseases that at the time were thought to be caused by viruses could
not be treated by eliminating nucleic acids, suggesting that the agent didn`t contain RNA or DNA. The theory
C
sc
states that normal PrP protein will convert to a diseased protein PrP which accumulates and leads to a fatal
neuronal degeneration without any signs of inflammation or immune response. In familial cases, a point
mutation in the prion gene explains disease susceptibility.
Classification
In humans
1. Creutzfeldt-Jakob disease (CJD) and its
varieties:
I.
Iatrogenic Creutzfeldt-Jakob disease (iCJD)
II.
Variant Creutzfeldt-Jakob disease (vCJD)
III.
Familial Creutzfeldt-Jakob disease (fCJD)
IV.
Sporadic Creutzfeldt-Jakob disease (sCJD)

In animals
1. Scrapie in sheep and goats
2. Bovine spongiform encephalopathy (BSE) in
cattle (known as mad cow disease)
3. Transmissible mink encephalopathy (TME) in
mink
4. Chronic wasting disease (CWD) in whitetailed deer, elk, mule deer and moose
5. Feline spongiform encephalopathy in cats
6. Exotic ungulate encephalopathy (EUE) in
nyala, oryx and greater kudu
7. Spongiform encephalopathy of the ostrich
Though this has not been shown to be
transmissible.

2. Gerstmann-Strussler-Scheinker syndrome
(GSS)
3. Fatal familial insomnia (sFI)
4. Kuru

Symptoms
Clinical features are dependent on the site and rate of deposition of PrP.
Creutzfeldt-Jacobs disease

Gerstmann-StrusslerScheinker syndrome
Fatal familial insomnia

Kuru

Initially non-specific symptoms: anxiety,

depression, dementia and memory loss
Later, with rapid onset: myoclonus, ataxia,
akinetic rigid state and seizures.
Death within 12 months is usual.
Non-specific: ataxia, Parkinsonism, dementia.
Death within 5 years.
4 stages
1. The patient suffers increasing insomnia, resulting in panic attacks,
paranoia, and phobias. This stage lasts for about four months.
2. Hallucinations and panic attacks become noticeable, continuing for
about five months.
3. Complete inability to sleep is followed by rapid loss of weight. This lasts
for about three months.
4. Dementia, where the patient becomes unresponsive or mute over the
course of six months. This is the final progression of the disease, and the
patient will subsequently die.
Papa, New Guinea.

Investigations and diagnosis

For CJD, the following measures are taken to confirm diagnosis.
CSF
-usually normal

EEG Bilateral high voltage sharp waves

on a background of slow wave activity

Pathology
The clinical picture and EEG suggest the diagnosis only ultimately
confirmed at post-mortem by autopsy of the brain.
Gross examination no change
Microscopically neuronal degeneration occurs with
marked astrocytic proliferation and amyloid plaque
formation. Vacuolization of glial cells results in
characteristic spongiform appearance.
Presymptomatic testing in sybjects with family history is
available.
Vacuolization typically
seen postmortem
Prognosis
No treatment is currently available, although one of the latest theories is aimed at finding the agent (possibly a
protein) which acts in the conversion to abnormal PrP protein and target it for treatment (Protein X)
Prions may play a role in the development of other neurodegenerative diseases such as Alzheimer`s disease,
Parkinson`s disease and motor neuron disease.

Slow virus infections

1. Progressive multifocal leukoencephalopathy (PML)
Definition:
A demyelination disorder caused by the JC virus dormanting in the oligodendrocytes.
Pathogenesis: A previous infection by the JC virus is reactivated.
Demyelination (oligodendrocytes) occurs in the subcortical white matter.
Symptoms:
Initially: Visual and mental impairment
Later: motor weakness develops.
Diagnosis:
CT & MRI are diagnostic lesions are seen in the periventricular position.
EEG: slow waves
Definitive diagnosis is by brain biopsy.
Treatment:
Interferon , cytosine arabinoside slow the progression
Prognosis:
Death within 6 months.
2. Subactue sclerosing panencephalitis SSPE
This is caused by measles. Children are mostly affected. Risk factors include acquiring primary measles at an
early age.
Pathogenesis: Incomplete virus that can not bud off from the cells.
Replicate in oligodendroglia + neurons (inclusion bodies), they later spread from cell to cell
chronic encephalitis.
Symptoms:
Stage I: cognitive decline decline attention, irritability
Stage II: motor decline ataxia, myoclonus, seizures, dystonias
Stage III: Spastic tetreaparesis, dementia
Permanent vegetative state Death
The condition may persist for more than 10 years.
Diagnosis:
EEG: periodic pattern with bursts every 3-8 seconds of high voltage, sharp slow waves,
followed by periods of attenuated (flat) background.
CSF: measles antibodies
Biopsy: inclusion bodies
3. Progressive rubella panencephalitis
Very rare manifestation of rubella infection. Rubella usually acquired at birth with signs of disease at age 8 19.
Mental and motor deterioration.
Resembles SSPE but rubella antibodies, no EEG signs, no inclusion bodies seen.
4. Acute disseminated encephalopmyelitis (ADEM)
Perivascular demyelination developing after viral infection (influenza, rubella, VZV)
There is fever headache, nausea, meningism, focal neurological signs, myoclonus, optic neuritis.
Diagnosis: CSF: protein, lymphocytes
EEG: generalized asynchronous slow activity
Treatment: steroids

10

Topic III/ 4 Neurological consequences of AIDS

General
HIV-1 virus has both lymphocytic (CD4 lymhocytes) and neurotropic (microglial) properties. Neurological
features develop in 80% of infected individuals, manifesting as either:
Direct effects of the HIV virus or infection
Tumours and vascular disorders associated with immunodeficiency
AIDS is the end stage of chronic infection and is defined as having less than 200 000 CD4+ lymphocytes per ml or
less than 14% of the total circulating lymphocytes when evidence of HIV-infection is established. In poor
countries, the definition is another because lack of equipment.
Clinical course of HIV infection
Acute infection

Seroconversion to HIV antibody + (4-12

weeks)
70%
Asymptomatic
Detected on antibody screening
Counseling
Prevention of spread

30%
Persistent generalized
lymphadenopathy hyperplasia
of neck lymph nodes

months or years
Aids related complex (ARC)
Investigations
HIV antibody +
HIV isolation
Lymphopenia
Thrombocytopenia
Lack of response to skin
antibody tests

Symptoms
Weight loss
Diarrhoea
Lethargy
Minor opportunistic
infections, e.g.
impetigo and oral
candida
Symptoms
Range of severe
opportunistic
infections and tumors
Presenting illness:
Pneumocystis carinii
pneumonia - 50%
Kaposi`s sarcoma
(multiple violaceous
skin lesions) 30%
Others 30%, e.g.
Mycobacterium
CNS lymphoma
Non-Hodgkin
lymphoma

Investigations
Results same as in ARC,
but cellular immunity
impaired.
T-cell lymphocyte
suppression especially
CD4 (helper subset) with
several of normal
CD4:CD8 ratio.

AIDS

11

Neurological presentation of HIV infection and diagnosis

CT/MRI
Cerebral tumors

AIDS dementia (in 15%)

Direct HIV infection with
demyelination and perivascular
inflammatory changes. Intellectual
decline of subcortical type

Primary cerebral
lymphoma
Metastatic systemic
lymphoma
Metastatic Kaposi`s
sarcoma

Infections
Encephalitis
CMV
Herpes
zoster/simplex
Toxoplasmosis
PML
Cerebral abscess
E.Coli
Aspergillus
Candida
Nocardia

Meningitis
HIV-1
Mycobacterium
Listeria
Syphilis
Aspergillus
Peripheral neuropathy
Herpes zoster
radiculopathy
Cauda equina
syndrome (CMV)
Acute reversible
demyelination
Chronic
demyelination

CT/MRI
Psychometry

CT/MRI
Antibody tests
Biopsy

Retinopathy

CT/MRI
Aspiration/culture
Antibody tests

Myelopathy

CSF exam
and culture
Antibody tests

Fundal exam
Antibody tests

CMV
Toxoplamosis

Spinal CT/MRI
Antibody tests

Acute reversible
Compression
Abscess
Systemic lymphoma
Ascending
CMV
Herpes zoster simplex
CT/MRI
Vascular disorders
Intracranial hemorrhage
Cerebral haemorrhage (septic
emboli or thrombotic)

Nerve conduction
studies
Antibody tests

Treatment

Opportunistic infections are treated as specific infections. Biopsy is avoided and trials of therapy is
administered, biopsy only if lesion does not resolve on CT (eg. Cerebral toxoplasmosis)
Zidovudine (AZT) prolongs survival by interfering with nucleic acid synthesis and prolongs survival.
Other drugs which can boost the immune system and/or interfere with the retroviral multiplication are
used.

12

Topic III/ 5 Clinical types and treatment of multiple sclerosis

Definition
Multiple sclerosis is an autoimmune, chronic demyelinating disease characterized by focal disturbance of
function and a relapsing and remitting course
Aetiology

The disease occurs most often

in temperate climates and
prevalence differs at various
latitudes (N)
Young adults (20-40 y.o)
Women: men 2:1
Immigrants adopt prevalence
rate if they travel before age 15
3% chance that a sibling or
parent is affected

Pathogenesis and pathology

Proposed causes
1. Disordered autoimmune response
2. Genetic predisposition
3. Environmental exposure (viruses
mycoplasma, measles, rubella,
mumps or HTLV III)
4. Age of individual at exposure
5. Sunlight exposure, vitamin D, diet

Demyelination may have 2 types of effects on

axonal conduction
Negative conduction slow conduction
(especially in response to high TC or
metabolic changes)
Positive conduction ectopic impulse
generation (spontaneous or following
mechanical stress)

Multiple scarred areas in the brain (plaques) confined to the

white matter.
Axons/neurons or oligodendrocytes/myelin
(the loss of one will effect the integrity of the other)

13

Symptoms

Of special notice

Retrobulbar neuritis typically on only one

eye. Opththalmoscope picture:

Lhermitte`s sign: with cervical posterior

column involvement sudden neck flexion
will evoke a shock-like sensation in the
limbs

Types of multiple sclerosis

85%

10%

14

Diagnosis
1. MRI
(cranial, spinal)

Positive in 90% of patients

More sensitive than CT
Brain stem, cerebellar,
spinal cord lesions
Distribution and
morphology of lesions
Not disease-specific
changes!
Predicitive value!

2. CSF examination

Useful in patients:
with atypical clinical
syndromes
with nondiagnostic MRI
with progressive course
without relapses

3. Evoked potentials

Visual evoked potential

(VEP)
Somatosensory evoked
potential
Brain stem evoked
potential
Motor evoked potential

New MS diagnostic criteria (lecture 2008)

Differential diagnosis
Metabolic disorders
Autoimmune diseases
Infections
Psychiatric disorders
Vascular disorders
Genetic syndromes
Lesions of post.fossa and spinal cord
Neoplastic diseases
Variants of MS

Disorders of B12 metabolism, leukodystrophies

Sjgren`s syndrome, Behcet`s disease
HIV and HTLV associated myelopathy, Lyme disease
Conversion reaction, malingering
Spinal dural AV-fistula, cavernous hemangioma
Hereditary ataxias and paraplegias, Leber`s optic atrophy etc.
Arnold Chiari malformation, spndolytic and myelopathies
Spinal cord tumor, CNS lymphoma, paraneoplastic disorders
Optic neuritis, Marburg disease etc

15

Treatment
1. Relapse
high dose methylprednisolone iv.
plasmapheresis
2. Disease-modifying therapies
- Interferon beta 1a (Avonex, Rebif) RRMS
- Interferon beta 1 b (Betaferon)
RRMS, SPMS with relapses
- Glatiramer acetate (Copaxone)
RRMS
- Mitoxantrone (Novantrone)
severe forms of RRMS, SPMS, PR
(combination therapy, adhesion-molecule blockade-Natalizumab, azathioprine, IVIg, bone marrow/stem cell
transplantation)
Symptomatic treatment
Spacticity (70% of patients!)
Baclofen (Lioresal) GABA analogue, maximum: 40-120mg/day
Tizanidine (Sirdalud) alpha-2 adrenerg agonist: maximum:36mg/day
Dantrolene (Dantrium) acts on skeletal muscle (rarely)
Botulinum toxin blocks the release of Ach in adductor spasm
Intrathecal baclofen : 300-800ug/day
Bladder dysfunction (75% of patients!) - history, resid.vol.measure!
Detrusor hyperreflexia: anticholinergs
oxybuynin (Ditropan, Oxytrol transdermal patch)
Tolterodine (Detrol)
Desmopressin (DDAVP, synth.analogue of Vasopressin)
Botulinum toxin
Sphincter-detrusor dyssinergy:
alpha-blockers, anticholinergs with intermittant catheterisation
Tremor (38% of pts, head, upper extremities)
CBZ, clonazepam, gabapentine, B6 vitamin,
thalamotomy, deep brain stimulation (DBS)
Paroxysmal symptoms
Carbamazepine, lamotrigine (Lamictal) trigeminal neuralgia
Depression
SSRI (citalopram, fluoxetine, sertraline), psychotherapy
Fatigue
amantadine, modafinil
Prognosis
Good prognosis
Female
Onset: relapsing-remitting
Complete recovery
Long inter-attack interval
Low frequency of attacks in early course
Long time to DSS3
Decreased age

Worse prognosis
Male
Onset: polysymptomatic / motor
Incomplete recovery
Short inter-attack interval
High frequency of attacks in early course
Short time to DSS3
Increased age

16

Topic III/ 6 Histopathological classification of brain tumors

General
A more precise term than brain tumors is intracranial tumors since neoplasms can arise from other tissues
than strictly neuronal brain tissue. Most intracranial tumors are caused by metastases. Often, the cause of
death is herniation and ICP. Brain biopsy is the best diagnosMc method.
Classification of brain tumors (Dept. of Neurology)
1. Neuroepithelial tumors (eg. astrocytoma)
2. Tumors of the peripheral nerves
3. Tumors originated from the meninges
4. Tumors of the hemopoietic system, affecting nervous system
5. Germinal tumors
6. Sellar tumors
7. Tumors, spreading from the surounding structures to the brain
8. Metastatic tumors
WHO classification of brain tumors (2009)

Astrocytic tumors most common primary brain tumor

Pilocytic
Astrocytoma (diffuse, infiltrative, fibrillary)
Anaplastic
Glioblastoma
Oligodendroglial tumors and mixed gliomas
Oligodendroglioma, well differentiated
Anaplastic oligodendroglioma
Mixed oligodendroglioma/astrocytoma
Mixed anaplastic oligodendroglioma/anaplastic astrocytoma
Glioblastoma with oligodendroglioma component
Ependymal tumors
Myxopapillary ependymoma
Ependymoma
Anaplastic
Choroid plexus tumors
Choroid plexus papilloma
Choroid plexus carcinoma
Neuronal and mixed neuronal-glial tumors
Ganglioglioma
Central neurocytoma
Filum terminale paraganglioma
Dysembryoplastic neuroepithelial tumor (DNET)
Pineal parenchymal tumors
Pineocytoma
Pineoblastoma
Embryonal tumors
Medulloblastoma malignant childhood tumor originating in cerebellar vermis
Supratentorial primitive neuroectodermal tumor (PNET)
Atypical teratoid/rhabdoid tumor
Meningeal tumors benign, often compressing rather than invading tissue
Meningioma
Atypical, clear cell, chordoid
Rhabdoid, papillary, or anaplastic (malignant)

17

WHO
malignancy
grading
1
2
3
4
2
3
2
3
4
1
2
3
1
3
1-2
2
1
1
2
4
4
4
4
1
2
3

i.

1. Neuroepithelial tumors (eg. astrocytoma)

Astrocytomas - graded from A 1 to A 4. The most malignant form is anaplastic
astrocytoma, Glioblastoma multiforme (A3-4)
In older patients. Localized in the hemispheres. High malignancy,
rapid growth, infiltrative spreading. Butterfly tumor, transcallosal
propagation.
Symptoms: seisures, focal signs, elevated intracranial pressure, headache,
psychiatric disorders (depression, behavioural, personality changes)
Dg: CT, MR. Necrotic, irregular tumor mass, marginal enhancement,
widespread perifocal oedema. Brain biopsy.
Treatment: surgical: total removal is not possible. Irradiation and chemotheraby
mav be added. High rate of recurrence, poor survival (maximum 1,5 year, average a few months)

ii.

Oligodendroglioma. Rare, hemispherial tumor. Usually calcificated. Slow propagation, not very
malignant, but sometimes transfers to malignancy, to Glioblastoma multiforme. Highly epileptogenic.
Symptoms: seisures, focal signs.
Dg: CT, MR. Calcificated, circumscribed mass, slight perifocal oedema.
Brain biopsy is diagnostic.
Treatment: surgical: total removal. Antiepileptic medication.

iii.
iv.
v.
vi.

Ependymal tumors
Chorioid plexus tumors within ventricles, may lead to increased CSF production.
Pineal tumors - Parinaud syndrome.
Embryonic tumors Most important: Medulloblastoma. The most malignant childhood brain tumor,
originated from the vermis of the cerebellum. Invasive, infiltrating growth, high risk of recurrence,
metastatizes by CSF.
Symptoms: headache, nausea, vomiting, dysbalance, frequent falling. Brainstem symptoms.
Dg: CT, MR. Enhancing, space occupying mass in the posterior fossa, causing CSF circulatory block,
hydrocephalus.
Treatment: surgical + Chemotherapy. Recently long (5-7 years)
Others: teratomas

vii.

2. Tumors of the peripheral nerves

Schwannoma Originated from the sheet of the intracranial segment of cranial nerves, especially VIII (vestibulocochlear, vestibular part) - Acustic neurinoma Cerebello-pontine angel tumor.
Usually localized to the intra-canalicular part of the nerve, later growing out, compressing brainstem. Slow
growth, benign tumor. May be bilateral, esp. in m. Recklinghausen.
Symptoms: worsening hearing loss, tinnitus (usually unilateral), vertigo,
later, peripheral facial nerve palsy, after growing out the canal, brainstem
or other cranial nerve signs.
Dg: MR. Enhancing, round, circumscribed tumor along the course of the
VIII. nerve. BAEP.
Treatment: surgical or chemotherapy (for smaller tumors).
18

Total recovery may be achieved.

3. Tumors originated from the meninges

Meningiomas In any age, but mainly in older persons, more frequent in females. Very slow growth (20-30
years), but may reach extreme sizes. Rarely turns into malignancy. May destroy bones of skull.
Originated from cells of the arachnoidea. May be anywhere on meninges, but there are typical sites:
Fronto-basal (olfactory groove, Foster-Kennedy syndrome)
Convexity. Sphenoid bone. Parasellar. Falx cerebri. Tentorium. Clivus.
Spinal.
Symptoms: depending on localisation. Epileptic seisures may occur. Dg: CT, MR.
Strong CM enhancement, well circumscribed, calcificated, highly vascularized tumor,
with no or sligh oedema.
Widely attached to the meninges.
Treatment: surgical, total removal if possible. Total recovery may be achieved.

CT with CM

4. Tumors of the hemopoietic system, affecting nervous system

Primary nervous system lymphomas B-cell, non-Hodggkin lymphoma. In immunsuppressed patients, mainly in
AIDS.
Dg: MR. Round-like, sometimes multiple lesions, usually close to CSF. Brain biopsy is necessary.
Treatment: corticosteroids decrease the size of the tumors.
5. Germinal tumors
6. Sellar tumors
Pituitary adenomas Originated from endocrine gland cells of the pituitary glands.
Micro or macro-adenomas. Intra or suprrasellar masses.
Hormonally active or inactive.
Symptoms: local signs (visual field defect, etc.), hormonal dysfunction
Hyperfunction
hyperprolactinaemia (galactorrhoea, amenorrhoea)
GH overproduction (acromegaly, giant growth)
ACTH overproduction (Cushing disease)
TSH overproduction (central hyperthyreoidism)
Hypofunction
Decrease of one or all the upper hormones (panhypopituitarism)
Caused by compression of the functioning normal gland tissue.
Dg: CT, MR. Microadenomas are non enhancing foci within the normal gland Tissue.
Macroadenomas are usually enhancing, irregular, masses, with extrasellar propagation.
Treatment: surgical: transsphenoidal or by craniotomy. Irradiation.
Hormonal treatment: bromocriptine may decrease the tumor size and normalize the hormonal dysfunction.

7. Tumors, spreading from the surounding structures to the brain

19

8. Metastatic tumors
In many cases the brain metastasis is diagnosed before the recognition of the primary tumor. Sometimes the
origin is not found at all.
Metastatis brain tumors, in order of frequency:
Lung
64%
Breast
14%
Unknown origin
8%
Malignant melanoma
4%
Colorectal
3%
Kidney
2%
Others
5%
Symptoms: not differing from the general tumor-symptoms.
Focal epileptic seizures are quite frequent.
Dg: CT, MR: often multiple, round like, enhancing lesions with large perifocal oedema.
Lumbar puncture (for diagosing meningeal spreading of the tumor carcinous meningitis)
Brain biopsy. May provide information about the origin of the tumor.
Investigation of the primary tumor.
Treatment: if the metastasis is solitary, surgical removal is possible. In multiple cases irradiation or
chemotherapy. Outcome is dependent on the general oncologic state of the patient.
Intracranial tumors according to location

20

Topic III/7 Brain tumors of childhood

1. Medulloblastoma
Age 5, highly malignant, cerebellar tumour, derived from primitive embryonic cells.
Symptoms
Cerebellar signs develop over a few weeks (trunk + gait ataxia)
ICP (headache, vomiting, papilledema, III paralysis, impaired consciousness)
Diagnosis
CT: isodense midline lesion in vermis, MRI is superior.
Management
o MRI + gadolinium
o CSF analysis
o Staging by bone marrow examination
o Surgery
o Radioptherapy (whole neural axis radiation)
o Chemotherapy
Prognosis
Prognosis is poor
75% 5 years survival after excision and irradiation (radiosensitive)
Severe CNS damage if the disease is survived.
Collins law: If medulloblastoma is radically removed, then the child can be regarded as
cured if she/ he survived his age + 9 months.
2. Cerebellar astrocytoma
Cerebellar hemisphere or vermis, extending to brain stem
Symptoms
Gait + trunk ataxia developing over several months
CSF obstruction may occur
Diagnosis
o CT: cystic area surrounded by low density matter
Management
Surgery
Prognosis
o Low grade tumor with excellent prognosis
3. Craniopharyngioma
Derived from Rathckes pouch. Cystic or solid.
Symptoms
Growth begins next to pituitary stalk, ICP, hydrocephalus, demenMa
Optic atrophy, bitemporal hemianopia
Hypothalamus dysfunction (dwarfism, Diabetes insipidus, etc)
Diagnosis
o CT/ MR
Management
Surgery + radiotherapy
4. Optic nerve astrocytoma
30% are associated with neurofibromatosis.
Symptoms
Nerve entrapment may occur, scotomoas developing into complete visual loss
Anterior expansion (orbit) propoptosis
Posterior expansion hydrocephalus, precocious puberty (if hypothalamus is inltrated)
Diagnosis
o Xray: bilateral dilated optic canal
o CT:
enhancing . mixed density lesion
o MR better for chiasmatic visualization
Management
Surgery

21

Topic III/8 Metastatic tumors of the brain

Metastatic tumors from other organs are the most common causes of intracranial, or brain tumors.
In many cases the brain metastasis is diagnosed before the recognition of the primary tumor found elsewhere in
the body. Sometimes the origin is not found at all.
MetastatiC brain tumors, in order of frequency:
Lung
64%
Breast
14%
Unknown origin
8%
Malignant melanoma 4%
Colorectal
3%
Kidney
2%
Others
5%
Symptoms common for all brain tumors
1. Focal signs
Direct effect of the tumor itself.
Damaged function (e. g. paresis, hypaesthesia, visual field defect, etc.)
Positive symptoms - focal or secondarily generalized epileptic seisures,
helpful in localizing the tumor.
2. Compression signs
o on surrounding structures, tracts, cranial nerves, CSF pathways resulting
in hydrocephalus.
3. General symptoms
caused by the increased intracranial pressure, mass effect of the tumor,
independent from its nature.
4. Psychic signs
o cognitive, behavioural or personality changes (sometimes leading or only
features of the tumor)
5. Hormonal changes
result of dysfunction of the pituitary gland.
(hyper or hypofunction)

Insidous development of symptoms is typical for brain tumors.

Sudden worsening or onset ot new symptoms may be a consequence ot intratumoral haemorrhage, or
herniation.
Focal epileptic seizures are quite frequent.

Sites of metastases
75% hemispheres
25% cerebellum
if CSF pathways are infiltrated hydrocephalus, malignant meningiMs

22

CT, no CM

CT with CM

CT with CM

Diagnosis
CT

MRI

Lumbar puncture

Brain biopsy

Investigation of the primary tumor

Single / multiple well demarcated lesions

(low density)
Extensive surrounding oedema
Contrast Enhancement
Shows small lesions, typically locating
between grey & white matter.
For diagnosing meningeal spreading of the
tumor carcinogenous meningitis
May provide information about the origin of
the tumor, in that way it is always the best
Histology etc

Treatment
If the metastasis is solitary, surgical removal is possible. In multiple cases irradiation or chemotherapy. Outcome
is dependent on the general oncologic state of the patient.
Symptomatic treatment
Oedema corMcosteroids (mannitol will not work for oedema surrounding tumour )
Seizures anMconvulsants
Surgery
Postoperative radiotherapy gliomas, radiosensitive metastasis

23

Topic III/9 Paraneoplasias of the nervous system

(PML, neuropathies, cerebellar degeneration, Lambert-Eaton sy.)
Definition
A syndrome directly resulting from a malignant neoplasm, but not resulting from the presence of tumor cells in
the affected parts. Most often caused by breast, lung or ovarian cancer. Some of these disorders are believed to
occur when cancer-fighting antibodies mistakenly attack normal cells in the nervous system.
Pathogenesis
The cancer fighting T-cells are believed to attack the nervous system as an autoimmune dysfunction.
Neurotoxins and viral infections caused by tumor are also proposed.

I.

II.

Inflammatory neural degeneration

Encephalomyelitis with loss of groups of
neurons (e.g. limbic encephalitis, brain stem
encephalitis)
Inflammatory destruction of sensory
neuronal cell bodies (neuropathy)

Non inflammatory degeneration

e.g. selective loss of Purkinje cells in subacute
cerebellar degeneration)

Symptoms general for paraneoplasias of nervous system

Difficulty walking
Difficulty maintaining your balance
Difficulty swallowing
Loss of muscle tone
Loss of fine motor coordination
Slurred speech
Memory loss

Vision problems
Sleep disturbances
Dementia
Seizures
Numbness and tingling in your arms and legs
Dizziness

Incidence
Paraneoplasia of the nervous system is a rare condition that affects < 1% of people with cancer.
1. Progressive multifocal leukoencephalopathy (PML)
Definition:
A demyelination disorder, caused by the JC virus dormanting in the oligodendrocytes.
Pathogenesis:
a previous infection by the JC virus is reactivated.
Demyelination (oligodendrocytes) occurs in the subcortical white matter.
Symptoms:
Visual impairment and mental impairment are initial signs.
Later motor weakness develops.
Diagnosis:
CT & MRI are diagnostic lesions are seen in the periventricular position.
EEG: slow waves
Definitive diagnosis is by brain biopsy.
Treatment:
interferon , cytosine arabinoside
slow the progression
Prognosis:
death within 6 months.

24

2. Neuropathies
The destruction of the nerve is associated with malignancy, it may be axonal, myelin, motor or sensory. It may
or may not be associated with abnormal serum paraprotein. Typically associated with kidney and bronchus
tumors
Guillain barre syndrome
(Acute demyelinating Polyneuropathy)

This is associated with Hodgkins disease. Ascending paralysis,

mild sensory loss in comparison to the motor loss. Arefelexia.
CSF protein is elevated. Pathology: segmental demyelination,
axonal sparing

Subacute sensory neuropathy (anti Hu)

There is an axonal damage. Paresthesias and pain, truncal

sensory ataxia. Anti Hu antibodies. Anti Hu antibody disease
causes limbic encephalitis

Chronic demyelinating Polyneuropathy

(Neuropathy with paraproteinemia)

Progression is slow or relapsing. Axons are spared.

Demyelination is segmental. Nerve conduction velocity is slow.
The M oligoclonal band (IgM) interacts with the myelin
associated glycoprotein (MAG)

Sensory motor neuropathy

Simply destroying the cell body

3. Cerebellar degeneration (anti YO antibodies)

A progressive disorder, characterized by truncal ataxia, associated with ovarian, breast cancer, Hodgkins
lymphoma.
Pathogenesis: anti purkinje cells antibodies (Anti Yo antibodies)
Pathology: loss of purkinje cells
Symptoms of cerebellar lesion: wide-legged and unsteady walk, vertigo, dysarthria, diplopia, nystagmus
There is dementia with no anatomical explanation.
Usually co-exists with Lambert-Eaton syndrome
4. Lambert-Eaton myasthenic syndrome
Pathogenesis:
destruction by an antibody of the voltage sensitive calcium channel located in the
presynaptic cleft of the neuromuscular junction impairment of Ach release from the
presynaptic nerve terminals.
It is typically caused by paraneoplastic syndrome caused by small cell carcinoma.
Symptoms:
Weakness, myalgias, fatigability,
most severe in lower extremities in the proximal muscles.
Ptosis, dysautonomic signs (sicca syndrome = dry eyes, mouth, impotence, diminished
sweating, orthostatic hypotension)
The hallmark is reduction in strength at rest with transient improvement in power on repetitive maximal
exertion. Tensilon test dont improve power.
EMG: motor unit potential is low at rest but increases (increment) with exercise or titanic stimulation.
(the opposite of myasthenia gravis).
Treatment:
gunethidine or aminopyridine (improves Ca influx)
Plasmapharesis
Remove underlying malignancy

25

Other conditions classified as paraneoplastic syndromes of nervous system

5. Encephalomyelitis
This condition involves inflammation of your brain and spinal cord. Symptoms can range from numbness to
respiratory failure.
6. Limbic encephalitis
In this disorder, portions of your brain swell, which can cause memory loss, drowsiness, confusion,
disorientation and seizures, among other signs and symptoms.
7. Myasthenia gravis
This disorder is characterized by weakness and rapid fatigue of any of the muscles under your voluntary control,
including those in your face, eyes, arms and legs. The muscles involved in chewing, swallowing, talking and
breathing may be affected as well. Myasthenia gravis is often associated with a tumor of the thymus gland
(thymoma).
8. Neuromyotonia
This condition also known as Isaacs syndrome is characterized by abnormal nerve impulses from the motor
neurons of your peripheral nerves. These impulses cause twitching, progressive stiffness, muscle cramps and
slowed movement, among other signs and symptoms.
9. Opsoclonus-myoclonus
Rapid, irregular eye movements (opsoclonus) coupled with quick involuntary muscle jerks (myoclonus) can result
from damage to your nervous system.
10. Stiff person syndrome
This disabling neurological disorder is characterized by progressive, severe muscle stiffness or rigidity, mainly in
your spine and legs. It may also cause painful muscle spasms.

26

Topic III/ 10 Disorders associated with parkinsonian syndrome

Parkinsonism (akinetic rigid syndrome) PD is the most common cause of chronic progressive Parkinsonism, a
term which refers to the syndrome of tremor, rigidity, bradykinesIa and postural instability.
Aetiology
Primary idiopathic
parkinsons disease
Genetic: Michale J.
Fox (earlier onset!)

Secondary parkinsonism

Drug induced (neuroleptics)

Toxic (MPTP, CO poisoning)
Wilsons disease
Post encephalitis
Parkinson plus syndromes (multiple system atrophy, progressive supranuclear
palsy)
Alzheimer disease
Diffuse Lewy body disease
Subcortical lacunar infarct (cerebrovascular disease)
Corticobasal degeneration

Symptoms/disorders
Initially patient complains
about pains and aches
Later
1. Bent (flexed posture)

3.Mask-like expressionless face, often

with drooling
4.Pill rolling tremor of hands

Starts unilat. Upper limb

spreads to all four limbs

2.Stiff, shuffling gait

4/sec.

Disappears during sleep

Improves on movement

5.Bradykinesia

Affects all movement from mastication to swallowing and slow deliberate gait. Festinant gait
means that the gait is difficult to initiate.

Excessive sweating and greasy skin (seborrhea)

Depression or drug induced confusional states occurs in 30% of patients.

Occasionally
autonomic
occur,demenMa,
such as postural
hypotension.
Progressive
supranuclear
palsy features
axial rigidity,
gaze palsy,
pseudobulbar palsy with dysarthria,
Pathogenesis

27

28

Topic III/ 11 Treatment of Parkinsons disease

Treatments and drugs

1. Medications
2. Physical therapy
3. Surgery
Initial response to medications may be very good, but diminish over time. Later, lifestyle changes, such
as physical therapy, a healthy diet and exercise, in addition to medications is currently recommended.
In some cases, surgery may be helpful.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of
dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.
Levodopa
The most effective Parkinson's drug is levodopa, which is a natural substance that we all have in our body.
When taken by mouth in pill form, it passes into the brain and is converted to dopamine.
Levodopa is combined with carbidopa to create the
combination drug Sinemet.
The carbidopa protects levodopa from premature
conversion to dopamine outside the brain; in doing
that, it also prevents nausea.
In Europe, levodopa is combined with a similar
substance, benserazide, and is marketed as Madopar.

2 downsides of Levodopa
Limited use due to wax and wane ("wearing off")
drug holiday
Drug Holiday
Withdrawal of the drug (3- 21 days)
Sensitivity of the receptors increase we can use
smaller doses and start over again!
Risk: Akinesia, may lead to pneumonia and embolism
Can only be done at a hospital

Side effects:
confusion, delusions and hallucinations, and
dyskinesia which can be controlled but at the expense
of reduced parkinsonism control

29

Dopamine agonists
Mimic the effects of dopamine in the brain

Not nearly as effective in treating the symptoms of Parkinson's disease.

However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.

Pills
Patches
Injection

Pramipexole (Mirapex)
Ropinirole (Requip)
Rotigotine (Neupro)
Pergolide (Permax) withdrawn, heart valve problems
Apomorphine (Apokyn) short acting for quick relief

The side effects

include those of carbidopa-levodopa, but less dyskinesia. However, they are substantially more likely to
cause hallucinations, sleepiness or swelling.
compulsive behaviour such as gambling, hypersexuality and overeating may occur.

MAO B inhibitors

Selegiline and rasagiline help prevent the breakdown of both naturally occurring dopamine and
dopamine formed from levodopa. They do this by inhibiting the enzyme monoamine oxidase B (MAO B)
the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious
interactions with other medications, including drugs to treat depression and certain narcotics.

Catechol O-methyltransferase (COMT) inhibitors

These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down
levodopa. Tolcapone (very hepatotoxic, on ly given when no response to other drugs) Entacapone
doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called
Stalevo.

30

Anticholinergics

These drugs have been used for many years to help control the tremor associated with Parkinson's
disease.

1.
2.
3.

Benzatropine
Biperiden
Procyclidin

However, their modest benefits may be offset by side effects such as confusion and hallucinations,
particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention
especially in men with an enlarged prostate and severe constipation.

Antivirals (unknown mechanism how they help)

Amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease.
Or added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease,
especially if they have problems with involuntary movements (dyskinesia) induced by carbidopalevodopa.
Side effects include swollen ankles and a purple mottling of the skin.
Physical therapy
Improve mobility, range of motion and muscle tone.
Improve your gait and balance.
Although specific exercises can't stop the progress of the disease, improving muscle strength can help you feel
more confident and capable.
A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is the most common surgical procedure to treat Parkinson's disease. It involves
implanting an electrode deep within the parts of the brain that control movement. The amount of stimulation
delivered by the electrode is controlled by a pacemaker-like device placed under the skin of the upper chest. A
wire that travels under the skin connects the device, called a pulse generator, to the electrode.
Deep brain stimulation is most often used for people who have advanced Parkinson's disease who have unstable
medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary
movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn't help
dementia and may make that worse.
Like any other brain surgery, this procedure has risks such as brain hemorrhage or stroke-like problems.
Infection also may occur, requiring parts of the device to be replaced. In addition, the unit's battery beneath the
skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn't beneficial for
people who don't respond to carbidopa-levodopa.

31

Topic III/ 12 Hyperkinetic movement disorders

1. Tremor
Rhythmic involuntary oscillating movements
1.Physiological
anxiety, caffeine, sleep deprivation, etc,
2.Resting tremor
parkinsonian type, associated with bradykinesia, rigidity commonly
in the distal limb (improves with anticholinergics)
3.Postural
can be familial, essential, senile (improved with benzodiazepines)
It is maximal when standing up.
4.Intention tremor
cerebellar lesions amplitude increases as target is being approached
5.Asterixis
appears as tremor, but it is intermittent inhibition of muscle
contraction (occurring with metabolic encephalopathies)
6.Benign essential tremor: 8Hz, common condition, inherited as an autosomal dominant trait.
It is worse in the upper limbs, head may be tremulous (titubation)
It is most apparent on posture (holding glass), it is not apparent on rest.
Treat with blocker or alcohol sips.
2. Chorea
Involuntary irregular jerking movements of limbs and axial muscle groups. It resembles restlessness since the
person has limited ability to suppress those movements
The main difference is that chorea has an unpredictable quality
1.Huntington chorea
Hereditary, trinucleotide repeat on chromosme 4 (huntingtin), characterized
by progressive chorea and dementia, developing in middle age, and
progresses to death within 12 years.
There is a neuronal loss in the Caudate & putamen. And reduction in
GABA & Ach level. Alleviation is achieved with phenothiazines.
2.Drugs
anti-psychotics (haloperidol)
tardive dyskinesia
3.Sydenhams chorea
associated with rheumatic fever in children, infections
4.Toxins
5.Metabolism abnormalities thyroid hormones, hypocalcaemia
6.Immune processes
SLE, PAN
7.Chorea gravidarum
8.Benedikts syndrome
Lesions of the rubrospinal tract
Contralateral tremor, ipsilateral III palsy,
Contralateral rigor (subtantia nigra)
Contralateral hyperesthesia for dorsal column modalities

3. Hemibalismus (subthalamic nucleus)

Unilateral violent limb flinging (patient who may hit him self).
It is the result of subthalamic nucleus (multiple sclerosis, post cerebellar artery, tumour)
Can be suppressed with haloperidol
4. Athetosis
The slowest type of dyskinesia, Present in childhood as slow writhing like movements, occurring in distal
muscles. Responding to anticholinergic drugs.
Hypoxic neonatal CNS injury, kernicterus, lipid storage diseases
32

Lesions of the neostriatum (Littles syndrome)

Rubrospinal tract (Benedikts syndrome)
5. Dystonia
Sustained abnormal posture due to contraction of large trunk / limb muscles
(e.g. spasmodic torticolis)

Dejerine Rousy syndrome (VPL of thalamus = nigrostriatal, thalamostriatal pathways)

Contralateral: hemiparesis, hemihypesthesia, hemiataxia, pain

Dystonia musculorum deformans. Inherited disease, common in Ashkenazi Jews.

Writers cramp

Spasmodic torticolis

Blepharospasm & oromandibular dystonia

Progressive supranuclear palsy

Treatment is botox injections every 3 months.

6. Myoclonus
Asymmetrical irregular shock like contraction.
Sleep, feeding baby
Causes
Progressive myoclonus Tay sachs, Gauscher
Metabolic
encephalopathy, Hyponatreamia, hypocalcaemia, hypoglycaemia
Degenerative:
Alzheimer, Huntington, CJD, SSPE
Miscellanous
HIV, vasculitis, sarcoidosis, paraneoplastic syndrome, CJD
Epilepsy
Treatment: clonazepam, pyracetam, levodopa

7. Tics
Spontaneous purposeless simple & complex movements or vocalizations that abruptly interrupt normal motor
activity. Always involving facial muscles
Gilles De tourette syndrome
Tardive dyskinesia
A movement disorder involving the face (lip smacking, grimacing, and facial contortions). It develops after
chronic exposure to neuroleptics (e.g. haloperidol).
It is temporary worsened when the offending drug is stopped. It is caused by increased D2 receptor density.
Slow movements
Athetosis / dystonia
Rapid movements
Controllable
tics
Uncontrollable
Distal
Chorea
Proximal
Ballismus
Multifocal
Myoclonus

33

Topic III/ 13 Differential diagnosis of tremor

Tremor is a rhythmic involuntary movement normally affecting the limbs. Diagnosis depends on examination of
the character of the tremor as well as the presence of other specific features.
Note the presence of tremor:

1.
2.
3.
4.

At rest
On maintaing posture
On movement (finger-nose test between target)

At the end of movement (finger-nose test at target)

Observe:
1. Rate
i. Slow (4-6 Hz)
ii. Fast (6-12 Hz)
2. Amplitude (fine or course)
3. Distribution ( head, trunk or limbs, distal or proximal)
4. Associated features (eg. Disorders of gait or balance)

Most tremors disappear during sleep

1. Physiological tremor

2.Pathological tremor

Characteristic pathological
tremor
Tremor at rest

Evident on maintaing a fixed posture,

its fast, fine in character, distal in
distribution, and non-disabling. It is
enhanced by fatigue, anxiety, drugs
eg caffeine or steroids
Occurs at rest or with movement,
slow in rate, course in character,
proximal or distal, and often
asymmetrical in distribution. This
tremor is socially and physically
disabling.
Disease association
Parkinson`s disease or drug-induced
parkinsonism

Tremor on maintaing posture and

throughout range of movement

Postural tremor

Tremor during and maximal at the

end of movement

Cerebellar intention tremor

34

Description
Pill rolling tremor,
decreasing with movement
o Rate: 3-7 Hz
o Amplitude: course
o Distribution: distal limbs
o Usually associated with
bradykinesia and rigidity
o Tremor absent at rest, but
there on maintaining
posture or movement
o Rate: 6-12 Hz
o Amplitude: fine
o Distribution: mostly upper
limbs
o Titubation tremor on head
on the trunk of ten present.
o Tremor absent at rest,
present during movement
and maximal on
approaching target, eg
finger to nose test
o Amplitude: course
o Distribution: proximal and

distal. Titubation may occur

Topic III/ 14 Classification of encephalopathies
General
Encephalopathy literally means disease or disorder of the brain. It may range from irreversible prion-caused
disease (transmissible spongiform encephalopathy) to reversible states such as nutritional deficiencies, toxins,
and several other causes.
Generally, recovery from progressive state of encephalopathy results in sequele of:
1) ataxia, 2) parkinsonism, 3) dementia, 4) hemiplegia. All depends on which structures was destroyed.
1. Metabolic encephalopathy
1. Hypoxia
Grey matter is more vulnarable, damage begins in watershed areas
Leads to petechial haemorrhages, oedema, necrosis, gliosis
2. Hypercapnia
3. Hypoglycaemia..
Sympathetic overactivity, confusion, motor signs, coma
4. Hyperglycaemia.
Can be diabetic ketoacidosis or hyperosmolar nonketotic hyperglycaemia.
Ketoacidosis insulin + K + P
Hyperosmolar nonketotic hyperglycaemia uids + insulin.
5. Hepatic.
Either mental state alteration or neurological disturbances
6. Uremic.
7. Pulmonary
Caused by hypoxia
8. Hyponatraemia
Brain cell swelling, seizures. Correction with hypertonic saline with
Furosemide. Complications of rapid therapy causes central pontine
myelinolysis (confusion, waudriparesis)
9. Hypercalcaemia
Constipation, vomiting, weakness. Seizures, short QT interval.
Treatment with hydration & furosemide
10. Hypocalcaemia.
Psychosis, Chvostek sign, carpopedal spasm following tourniquete
induced limb ischaemia (Trousseus sign). Seizures, laryngospasm.
Treatment: calcium gluconate.
11. Hypothyroidism.
Disruption of the neuronal metabolism. T3, T4, TSH.
Associated with hyponatraemia & hypoglycaemia.
12. Hypoadrenalism
hyponatraemia, hypoglycaemia, low bicarbonate. hyperkalaemia
,
(Addisons).
treate with hydrocortisone,
13. Hyperadrenalism
Hyperglycaemia, hypernatraemia hypercalcaemia,
(Cushing).
2. Toxic encephalopathy
Wernicke encephalopathy (alcohol)
Reyes syndrome: virus + salicylate + genetic predisposition mitochondrial damage brain oedema
+ liver damage
o Heavy metal: Lead
o
o

3. Demyelinating encephalopathy
4. Hypertensive encephalopathy

o
o
o

5. Infectious encephalopathies
HIV
Prion disease
Viral
6. Traumatic encephalopathy
.
35

Topic III/ 15 Primary degenerative dementias

Definition of dementia (ICD-10, 1992)
A decline over at least 6 months in memory, deterioration in judgement and thinking, absence of clouding of
consciousness, decline in emotional control or motivation or change in behaviour.
Pseudodementia a depressive condition, mimicking dementia.
Differentiation of subcortical and cortical features

Subcortical

Cortical

Processing , retrieiving of information is slowed

The stored information is lost

Thinking

Slow

Normal

Speech

Normal, anomic

Amnestic, sensory aphasia,

paraphasia

Articulation

Dysarthric

Normal

Visuo-spatial
ability

Disturbed map reading

Disturbed copying of simple figures

Short term
memory

Preserved

Impaired

Long term
memory

Preserved

Gradual impairment

Personality

Apathy
Depression

Indifferent, relatively normal

Moria

Sometimes

Never

Gait

Depends on the pathology

Normal

Hyperkinesias

Tremor, chorea, dystonia

Non

Tone

Abnormal (hyper/hypo)

Initially normal

Diseases

Huntington
AIDS
Wilson
Multi infarct dementia

Hemispherical infarcts
Alzheimer

Classification

Miscellaneous causes of dementia

a. Alzheimer disease
b. Picks disease
c. Lewy body disease
d. Corticobulbar ganglionic degeneration
e. Parkinsons disease
f. Progressive supranuclear palsy
g. Huntingtons disease
1. Vascular dementia
2. Demyelinating disease
3. Neoplasm
4. Normal pressure hydrocephalus (NPH)
5. Vasculitis
6. Infections: syphilis, AIDS, Lyme, Whipples disease
7. Slow virus/prions: PML, SPPE, CJD, Gesterman straussler, FFI
8. Metabolic disorders: hypoxia, uraemia, hepatic failure,
endocrine, anaemias, vitamin deficiency
9. Toxic substance: alcohol, polydrug abuse, heavy metals
36

Alzheimers disease (AD)

Definition:
a subtle onset of memory loss followed by a slowly progressive dementia that has a course of
several years, microscopic plaques of A amyloid protein in the neuron, blood vessels.
Epidemiology
This is the most common cause of dementia in western countries.
10% of all 70 year olds have impaired memory, half of those have alzheimers disease (AD)
Aetiology
Genetic factors:
30% are familial
APP gene mutation (21) - trisomy 21 more gene dosage (1more chromosome)
Apolipoprotein E4 (chr 19)

amyloid
Exposure to aluminium
Pathology:
senile plaques (dystrophic nuerites clusters round a core of amyloid protein)
the amyloid derives from the APP.
Neurofibriliary tangles (derive from microtubule associated protein tau)
clinical manifestation
0
entorhinal stage: no dementia
I
Early stage:
memory loss, followed by slow deterioration of cognitive function
Limbic state
II
Middle stat:
isocortical state
patient is unable to work, he gets easily confused and lost
social behaviour is preserved
Language becomes impaired (aphasia, inability to name or identify objects)
Apraxia (sequential motor tasks, e.g. copying geometric tasks)
Cortical blindness (neuropathological changes in the visual cortex)
Hallucinations & delusions
Impaired sleep-wake pattern
Motor: muscle rigidity
III
End stage:
rigidity, mutism, incontinence
Eating, dressing, toilet require assistance
Hyperactive tendon reflexes
Primitive sucking, snouting reflexes
Myoclonic jerks
Duration of disease:

10 years (1-25 years)

Cause of death: malnutrition

Infections
Heart disease

37

Differential diagnosis
o Dementia
o Thyroid disease
o Vitamin deficiencies
o Brain tumour
o Drug intoxication
o Severe depression
Diagnosis:

Clinical picture & history

Mini mental test:
Orientation
time (hour, day, month, date, year)
Place (floor, place, city, country, hospital)
Registration
memorize 3 items
Calculation:
serial seven
Recall:
what was the 3 numbers
Language:
naming
Repetition
Understand commands
Reading
writing
Copying
MRI
Changes are seen in advanced stages
atrophy of hippocampus, diffuse cortical atrophy
EEG
Normal or show non-specific slowing
CSF
Normal, Ach, A amyloid levels, tau protein

Pathogenesis:
Order of damage: entorhinal cortex limbic system cortex (parietal temporal)
Early affected structures: parietal cortex
Temporal cortex
Hippocampus
Nucleus basalis (source of Ach in the CSF)
There are neurofibriliary tangles of a tau protein which is a microtubule associated protein.
There are several genes associated with the disease
21 chromosome (down syndrome patient exhibit similar pattern as in AD patients)
Presenilin 1 gene
Presenilin 2 gene (American families & Volga german ethnic background)
Apo E gene
Treatment:
Tacrine (tetrahydroaminoacridine) a cholinesterase inhibitor
Dinepezil, rivastigmine

38

Picks disease
A rare cause of dementia, mostly affecting females (40-60 year old)
The cerebral atrophy is greater than seen in Alzheimer Disease.
The atrophy is asymmetrical and more pronounced over the frontal lobe+/- temporal lobe
Pick bodies are found within the neural cytoplasm,
Cause is unknown, but there is an autosomal dominant transmission in some families.
The disease is hard to differentiate from AD, but frontal signs are more pronounced then, EEG is normal, CT
shows fronto-temporal atrophy
Death occurs within 5 years, not treatment is available.
Huntingtons disease (Chorea subcortical dementia psychosis frontal release)
An autosomal dominant, tirnucleotide repeat disease.
GABAergic and cholinergic cells are lost in the striatum. there is also loss of cholinergic neurons in the cortex
(deep layers of the fronto-parietal lobes). chorea start in the face and progress to the fingers and
limbsdementia & psychiatric abnormalities appear after and death.
All aspects of memory are impaired in early stage
Diffuse Lewy bodies disease
These are intracytoplasmic inclusions.
Cognitive decline without early memory impairment.
Fluctuating cognitive ability, parkinsonism, visual hallucinations.
Respond well to cholinesterase inhibitor (donezepil)
Corticobasal ganglionic degeneration
Parkinsonism
Symmetric cortical motor/sensory dysfunction: vision, speech, limb apraxia
Progressive supranuclear palsy
Definition:
Gaze palsy, extrapyramidal signs, axial dystonia, progressive pseudobulbar palsy
Aetiology:
unknown
Pathogenesis: The disease is confined to the subcortical grey matter.
Neuronal loss in the periaqueductal grey, brain stem, subthalamic nucleus
superior colliculus
Signs
Rigidity & dystonia (subthalamic nucleus)
Gaze palsy initially down, later to all direction (Superior colicullus, brain stem)
Progressive pseduobulbar palsy (brain stem)
hyperreflexic jaw, gag reflexes
weak palate, dysarthria, dysphagia
central XII palsy
Emotional liability, dementia.
Treatment:
none
Death within 5 years.

39

Topic III/ 16 Dementia in cerebrovascular disorders

Cerebrovascular events are the second most common cause of dementia. It is possibly reversible with the right
treatment. Vascular dementia is a heterogeneous entity with a large clinicopathological spectrum that has been
classically linked to cortical and subcortical ischemic changes resulting from systemic, cardiac, or local large- or
small-vessel disease occlusion. Thus, the diagnosis of vascular dementia is usually made on the basis of clinical,
neuroimaging, or neuropathological evidence of cerebral ischemia in the presence of progressive cognitive
decline. On the other hand, vascular pathology often coexists with Alzheimer disease, and this poses an
additional diagnostic challenge. This has led to the existence of the diagnostic term of mixed dementia.
Diagnostic criteria
1) Sudden dementia stepwise deterioration 2) Focal signs 3) CT/MRI findings
Probable VaD
Dementia
Focal neurological signs,
CT/MRI is supportive
The onset of the dementia
is sudden (within 3
months after the stroke),
stepwise deterioration.

Possible VaD
Dementia
Focal neurological signs,
CT/MRI is not prepared
No causal link between
the two disorders

Definite VaD
Probable +
neuropathology

Chronic Subdural Haematoma

Risk factors: elderly, cerebral atrophy, anticoagulant therapy, shunt
On CT: Isodense until 3 weeks hypodense
Signs: headache, dementia, fluctuating consciousness, ICP, focal neurological signs.
Management:surgical drainage.
Multi-infarct dementia (lacunar state)
Risk factors:
Hypertension, DM, coagulopathy, cardiovascular disease, previous infarcts.
Strategic places: angular gyrus Wernicke aphasia
MD thalamus ARAS (consciousness)
basomedial temporal lobe declaraMve memory loss
ACA territory motor / sensory cortex of legs
frontal lobe (release signs)
caudate, putamen (rigidity, bradykinesia)
head of caudate. chorea
CT: hypodensity, non enhancing
Binswanger disease (subcortical arteriosclerotic encephalopathy)
Progressive dementia + pseudobulbar palsy + diffuse hemisphere demyelination.
High plasma viscosity, hypertensive atherosclerosis chronic ischaemia in white maRer
CT: periventricular low attenuation
MRI: hyperintense on T2

40

41

Topic III/ 17 Multisystem atrophy

This is a group of neurodegenerative disorders affecting the autonomic nervous system and have several clinical
features of Parkinson`s disease and are often referred to as Parkinsonism plus syndromes
The 3 cardinal features of MSA
1. Parkinsonism
2. Autonomic failure, including
a. orthostatic hypotension
b. erectile dysfunction
c. urinary incontinence or retention
3. Cerebellar ataxia (failure of muscular coordination)
Classification
1. Shy-Drager syndrome (autonomic dysfunction)

The first recognized MSA, and has later been subclassified with 2 and 3 as MSA.
o Parkinsonism combined with autonomic failure.
o Parkinson features may respond to L-dopa, but the resulting orthostatic hypotension
often forces withdrawal of the drug.

2. Olivopontocerebellar atrophy (OPCA)

o The range of symptoms that can arise are many, including:
o Ataxia
o Chorea (irregular, spasmodic, involuntary movement of the limbs or facial muscles)
o Degeneration of the retina
o Dysarthria (difficulty articulating words)
o Dystonia (abnormal muscle tension)
o Kinetic tremor
o Neuropathy
o Spasticity (state of increased muscular tone with exaggerated tendon reflexes)
o Weakness
3. Striatonigral degeneration
o Parkinsonism (bradykinesia, rigidity) with no tremor!
o No response to medication
Pathology:
Neuronal degeneration in brainstem, cerebellum, striatum, intermediolateral cell column of the thoracolumbar
spinal cord.
Symptoms:
In genereal, the type of MSA is determined mainly upon which clinical symptoms predominate:
Autonomic dysfunction Shy-Drager syndrome
Cerebellar ataxia Olivopontocerebellar atrophy
Parkinsonism Striatonigral degeneraMon
Diagnosis.
Based on clinical findings (especially the irresponsiveness to L-Dopa) Orthostatic hypotension (often primary
presenting sign), heart rate variation with deep breathing, valsalva maneuver, Sudo motor function, cold
pressor test.
Treatment

42

Medications: the Parkinson-symptoms can not be treated by L-dopa in MSA. Raising blood pressure, reducing
Parkinson's-like signs and symptoms, pacemaker, impotence drugs, steps to manage swallowing and breathing
difficulties, bladder care are key words.. Slow progression of disease, but usually death within 10 yrs.
Topic III/ 18 Disturbed cerebrospinal fluid circulation (hydrocephalus)
Hydrocephalus is an increase in the CSF volume, usually resulting from impaired absorption. It is characterized
by ventricular expansion secondary to to brain shrinkage from a diffuse atrophic process (hydrocephalus ex
vacuo)
Normal CSF physiology
Function
1. Protection against mechanical trauma
2. Reservoir function in the regulation of the Intracranial pressure
3. Nutrients
4. Removal of metabolites
5. Pathway for pineal secretion to reach the
pineal gland
Formation
1. Choroid plexus (ependymal cells)
2. Ependymal cells lining the ventricles
3. Secretion rate of 0.5ml/min
4. Total volume of 140ml
5. Total turnover time is 5 hours

Circulation
About 1/5 of CSF is found in the
ventricles, the rest is surrounding the
brain. CSF is filtered into the dural
sinuses via the arachnoid granulations
(Pacini`s). The dural sinuses leads to the
jugular vein which connects to the
systemic venous system.
Choroid plexus lateral ventricles
third ventricle intervenMruclar
foramina cerebral aqueduct fourth
ventricle spinal canal

43

Absorption
Absorption is through the arachnoid granulations, which projects into to the dural venous sinus
Predilection places for obstruction

Hydrocephalus
Obstructive
flow obstruction within the
ventricular system

Communicating
impaired flow outside the
ventricular system

Normal pressure hydrocephalus

Aetiology
Acquired

1. Aqueduct stenosis
(infection)
2. Intraventricular
haematoma, abscess
3. Tumours (pineal,
choroids)
4. Tentorial herniation

Congenital

1. Aqueduct stenosis
2. Dandy walker (magendi +
Lushka atresia)
3. Arnold - Chiary
malformation (tonsilar
downward displacement)

Communicating
(the CSF outwith the ventr.system,
communicating with the
subarachnoid space)
1. Thickening of the
leptomeninx (infections,
subarachnoid
haemorrhage, trauma)
2. CSF viscosity (high
protein)
3. CSF synthesis (choroid
papiloma)

Consequences
Ventricular dilation CSF permeates into perivenricular white maRer (intersMMal oedema) ICP,
white matter damage, gliotic scarring

44

Clinical features
Children
o Head expansion
o Massive ventricular dilation
o Setting sun: lid retraction no upward gaze
(superior coliculus)
o Acute onset: consciousness, vomiMng
o Failure to thrive, mental retardation

Adults
Acute onset
o ICP (headache, vomiting, papiloedema,
consciousness, no upward Gaze)
Gradual onset dementia
o Gait ataxia
o Incontinence
Slow progression normal pressure hydrocephalus
(NPH)
o Dementia + gait ataxia + incontinence +
normal ICP
o Caused by : subarachnoid haemorrhage,
meningitis, trauma, 50% idiopathic
o Intracranial pressure monitoring: waves
o Treatment: shunt

Investigation
Skull X ray
size, suture width
CT
Ventricular enlargement
Periventricular lucency a sign of ICP
US
In infants
MRI
the same picture as in CT, more sensitive to periventricular lucency
ICP monitoring ( waves, plateau waves)

Management
Acute deterioriation

Gradual deterioriation
Arrested hydrocephalus

o
o
o

Ventricular drainage
Ventriculo-peritoneal or ventriculo-atrial shunt (if peritoneal adhesions)
Lumbar puncture if communicating hydrocephalus (eg following
subarachnoid haemorrhage
o
o

VP (ventriculoperitoneal) shunt
Removal of mass lesion if present
Symptomless ventr.dilation requiress no treatment, but close monitoring

45

Topic III/ 19 Syndrome of brachial plexus damage

Disease of a single peripheral- or cranial nerve is termed mononeuropathy, mononeuropathy multiplex is when
single nerves are damaged one by one. Several systemic diseases are associated with these conditions:
DM, sarcoidosis, rheumatoid arthritis, polyarteritis nodosa.

Root
injury

Dermatome pain

Muscles supplied

Movements weakness

Reflex

C5

Lower lateral aspect of

upper arm

Deltoid, biceps

Shoulder abduction,
elbow flexion

Biceps (5,6)

C6

Lateral aspect of
forearm

Extensor carpi radialis longus

& brevis

Wrist extensors

Brachioradialis

C7

Middle finger

Triceps and flexor carpi

radialis

Extension of elbow and

flexion of wrist

Triceps (7, 8)

C8

Medial aspect of
forearm

Flexor digitorum
superficialis&profundus

Finger flexion

None

Different brachial plexus lesions

1. Upper plexus lesions (C5-C6)
o Waiters tip hand
2. Posterior cord lesion (C5-C8)
o Extensor paralysis
3. Lower plexus lesions (C8-T1)
o Claw hand
4.
5.
6.
7.

Total brachial lesion

Brachial neuritis
Pancoast tumour
Thoracic outlet syndrome

46

1. Upper plexus lesions (C5-C6) Waiters tip hand

Aetiology:
Erb Duchene paralysis (trauma at birth)
Paralysis:
Deltoid, supra/infranspinatus (shoulder lift)
Biceps, brachialis (Elbow flexion)
Sensory:
C5, C6
Patient:
The arm is held internally rotated, extended arm, pronated forearm
Reflexes:
Biceps, radial
2. Posterior cord lesion (C5-C8) Extensor paralysis
Paralysis:
Extensors of finger, wrist, elbow (triceps), deltoid
Patient:
flexed finger, drop hand, flexed arm.
Reflexes:
biceps, radial, ulnar, triceps
3. Lower plexus lesions (C8-T1) Claw hand
Aetiology:
Klumpke`s paralysis or trauma (forced arm abduction at birth)
Paralysis:
Claw hands (intrinsic hand muscles)
Flexor / extensors of the long finger
Horners syndrome
Sensory loss:
C8-T1
4. Total brachial lesion
Complete flaccid paralysis, anaesthesia, Horner syndrome (T1 involvement)
5. Brachial neuritis (Neuralgic amyotrophy)
Cause
Idiopathic
Viruses (Cox, EBV, CMV), immunization (tetanus, influenza) as part of Guillain Barr
Strenous exercise or IV heroin abuse
Clinical
Acute onset shoulder pain, proximal weakness, muscle wasting, reex, minimal
feat
sensory loss. Recurrent episodes can occur, especially if family history.
Diagnosis Slowed conduction
Treatment Analgesia, steroids, physiotherapy
Prognosis full recover within 3 years
6. Pancoast tumour
Lower cervical & upper thoracic roots are affected by this apical lung tumor (usually sq.cell carcinoma)
Severe pain around the shoulder & arm, weak wasted hand muscles, paralysis and Horner`s syndrome.
7. Thoracic outlet syndrome
Aetiology: cervical rib, fibrous band.
Compression of the plexus, subclavian artery/vein
Clinical: Pain over the neck, shoulder, paralysis over the thenar & interosseous
Single limb Raynauds phenomenon, no radial pulse on abduction + external rotation (Ansons sign).
Diagnosis: MRI, X-ray, EMG, angiography
Winged-scapula long thoracic serratus ant.

47

Topic III/ 20 Syndrome of radial, ulnar and median nerve damage

Mononeuropathies
Nerve
Accessory nerve
Long thoracic
Suprascapular

Root
C3,C4
C5-C7
C5-C6

Muscle innervation
Trapezius muscle
Seratus anterior
Infra / supra spinatus

Axillary

C5-C6

Deltoid, teres minor

Musculocutnaeous

C5-C6

Corachobrachialis, brachialis,
biceps

Nerve

Root

Etiology

Radial nerve
Wrist drop

C6-C8

IM
injection
humeral
fractures
sleeping
on the
hand for a
the whole
night

Median nerve
Ape hand

C7-C8

Ulnar nerve
Claw hand

C7-C8

Muscle innervations
and restriction
Triceps, brachioradialis, extensors of
digits, abductor policis longus
wrist drop, flexed fingers

No abduction, apposition of thumb

Pronation of forearm (pronator
teres)
Ulnar deviation of wrist (paralysis of
flexor carpi radialis)
Flexor carpi ulnaris, Flexor digitorum
profundus
Adductor policis, Interosseous
opens the digit minimi
No adduction/abduction of the
fingers (interosseous)
No Thumb adduction
Claw hand

Radial tunnel syndrome

Compression of a branch of the radial nerve at the forearm. It is a pain-only
problem without motor or sensory changes. Pain on both sides of elbow, loss
of finger strength and pain doing twisting movements.
Carpal tunnel syndrome
compression of the median nerve in the carpal tunnel. The median nerve
provides sensation to the palmar side of the thumb, index finger, long finger
and radial half of the ring finger.

48

Movement (restriction)
Shoulder shrugging
Winging scapula
External rotation of the
arm, abduction of the
arm
Shoulder abduction)
No flexion, supination

Sensory
Dorsum of hand (7 sides from
thumb), forearm, arm

Sensory loss over the 3 sides

from digit minimi

Cubital tunnel syndrome

compression of the ulnar nerve at the elbow. Symptoms include pain and
paresthesias over the medial forearm and hand as well as weakness in the
ulnar nerve distribution Carpal tunnel syndrome

Topic III/ 21 Syndrome of lumbosacral plexus damage

The Lumbar plexus
Lies on the psoas muscle
T12-L5
Femoral n. (L2-L4)
Obturator n. (L2-L4)

The Sacral plexus

Lies in posterior pelvic wall
L5-S3
L4-S2
Tibial n.
L4-S2
Common peroneal
S2-S3
Pudendal plexus

Root
injury

Dermatome pain

Muscles supplied

Movements weakness

Reflex

L1

Groin

Iliopsoas

Hip flexion

Cremaseter

L2

Anterior aspect of thigh

Iliopsoas, sartorius, hip

adductors

Hip flexion, hip adduction

Cremaseter

L3

Medial aspect of knee

Iliopasoa, sartorius,
quadriceps, hip adductors

Hip flexion, knee

extension, hip adduction

Patellar

L4

Medial aspect of calf

Tibialis anterior, quadriceps

Foot inversion, knee

extension

Patellar

L5

Lateral aspect of calf

Extensor hallucis longus,

extensor digitorum lognus

Toe extension, ankle

dorsiflexion

None

S1

Lateral edge of foot

Gastrocneumius, soleus

Ankle plantar flexion

Ankle jerk

S2

Posterior part of thigh

Flexor digitorum longus,

flexori hallucis longus

Ankle planter flexion, tow

flexion

None

Etiology
1) Extension of disease from abdominal / pelvic organs
2) Postoperative
3) Radiotherapy
4) Compression by an aneurysm, tumour
5) Neuritis, DM

49

The proximity of the plexus to important

abdominal and pelvic structures renders
it liable to damage from disease of
these structures

Symptoms
Upper plexus lesions
Weakness of hip flexion and
adduction

Lower plexus lesions

Weakness of posterior thigh
(hamstrings) and foot muscles with

Anterior leg sensory loss

Posterior leg sensory loss

Both : severe burning pain that is worsened by coughing, sneezing etc.

Femoral nerve (L2- L4)

Obturator nerve (L2-L4)
Sciatic nerve (L4-S2)
Common peroneal (L4-S2)
Tibial nerve (L4-S2)

Mononeuropathies
Normal functions
hip flexion, leg extension,kicking
adduction, external rotation (leg crossing) leg crossing
hip extension, knee flexion
foot drop and heel walking
cant stand on toes (tarsal tunnel syndrome) toe walking

Femoral nerve
(L2-L4)
Iliopsoas, quadriceps femoris, pectineus, sarotius
Impaired: thigh flexion, leg extension
no knee jerk
sensory: anterior / medial leg + thigh

Obturator nerve (L2-L4)

Obturator external, adductor magnus, gracilis
50

Impaired: hip adduction + external rotation (no leg crossing)

Sensory: inner side of thigh

Sciatic (L4-S3)
Biceps femoris, semi membranous / tendineous
Impaired: leg flexion, no Achilles tendon reflex
Sensory: outer leg

Peroneal (L4-S2)
Peroneal muscles, tibialis anterior, extensor digitorm / halucis
impairment:
foot dorsiflexion, eversion (foot drop)
Sensory: dorsum, outer lower foot
Tibial (L4-S3)
Impaired plantar flexion, inversion (cant stand on toes)
No achiles tendon reflex
Tarsal tunnel syndrome Mbial nerve entrapment bellow medial malleoulus
sensory: sole
Superior gluteus nerve (L4,5 S1)

Inferior gluteus nerve (L4,5 S1,2)

Other nerves
Deep peroneal (inversion, dorsiflexion)
51

Superficial peroneal (eversion)

Tibial (post. Muscles of the leg)
Semitendinosus, semimembranosus, long head biceps, adductur magnus
Gastrocnemius, popliteus, plantaris, soleus, tibialis post. All flx
Med. plantarthenar mm., 1 lumbrical, skin of 1-7
st

Lat. plantarskin 8-10

Topic III/ 22 Etiology of polyneuropathies
Definition
Polyneuropathy is the simultaneous malfunction of many peripheral nerves throughout the
body.Polyneuropathies are classified according to:

Mode of onset

Functional or pathological type

Distribution

Causation
Mononeuropathy
- 1 nerve affected.
Mononeuritis multiplex - multiple nerve involvement in an asymmetrical manner
Polyneuropathy
- diffuse, symmetrical disease process that is usually distal with some proximal
progression

Etiology
HSMN chronic (months-years)
1. HMSN I
Demyelination / remyelination (adults)

2. HMSN II
Axonal loss
3. HMSN III
Demyelination / remyelination (children)
4. Refsums disease
Phytanic acid
Inflammatory demyelinating neuropathies infective neuropathies acute (days-4 weeks)
1. Guillain barre
2. AIDS
3. Leprosy
4. Diphtheria
5. Sarcoidosis
Systemic disease neuropathies chronic
1. DM
2. Renal disease
3. Carcinomatous
polyenuropathies
(myeloma, lymphoma)
4. CT & vasculitidies (SLE,
PAN, RA, Sjrgrens,
Scleroderma, Wegener)
5. Porphyria ( ALA)
6. Amyloidosis
7. Alcoholic polyneuropathy
Nutritional deficiency subacute (weeks)

52

1.

Thiamine (B1) - Beriberi

(dry=neuropathies,
wet=oedema)
2. Pyridoxine (B6)
3. B12
4. Vitamin E
Drugs & toxins subacute
1. Isoniazied, dapsone, hydralazine
2. Alcohol, Lead, Arsenic, Organophosphates
Patterns of nerve injury
1. Wallerian degeneration
Axons degenerates distally, following section
or severe injury, with degeneration of the
myelin. The process occurs within 10 days of
injury and this portion of the nerve is
inexcitable electrically. Regeneration can
occur if the basement membrane of the
Schwann cell survives and acts as a skeleton
along which the axons re-grows up top a
rate of about 1mm/day

2. Segemental demyelination
Scattered destruction of the myelin sheath
occurs without axonal damage.
The primary lesion affects the Schwann cell
and causes marked slowing of conduction or
conduction block. Prognosis for recovery is
good because the muscle is not denervated.

Normal myelin sheath!

3.Distal axonal degeneration

53

Damage to the cell body or to the axon will

affect the viability of the axon which will
die back from the periphery. Loss of
myelin sheath occurs as a secondary event.
Recovery is slow because the axon must
regenerate. When the cell body is destroyed
reinnervation of muscle can only occur from
surrounding nerves.

Nerve fiber types

Fiber type
Function
Type A
Alpha ()

Diameter
(mm)

Myelination

Conduction
velocity (m/s)

Sensitivity to
block

12-20

thick

70-120

5-12

thick

30-70

++

3-6
2-5

thick
thick

15-30
12-30

++
+++

Preganglionic

<3

thin

3-15

++++

Pain
postganglionic

0.4-1.2
0.3-1.3

none
none

0.5-2.3
0.7-2.3

++++
++++

Proprioception, motor
Touch pressure

Beta ()
Gamma ()
Delta ()
Type B
Autonomic
Type C
Dorsal root
Sympathetic

Muscle spindles
Pain, temperature

Symptoms of peripheral nerve disease

Sensory symptoms
Negative symptoms (loss of function)
proprioception
diculty in discriminaMng touch
feet & hands feel like coRon wool
gait unsteady through loss of posiMon sense (especially at night when vision cannot compensate)
Small unmyelinated fibres
pain, TC

54

Positive symptoms (gain of function - paraesthesias)

Large myelinated fibres
paresthesia (pins & needles)
Small non myelinated fibres
burning
dysaesthesia (pain on gentle touch)
hyperalgesia lowered threshold to pain
hyperpathia pain threshold is elevated, but is excessively felt
lightening pain sudden, very severe, shooting pain, which usually suggest a diagnosis of tabes dorsalis
(syphilis)
Motor symptoms
fasciculations, weakness
st
st
1 muscles arm 1 dorsal interosseous, leg external digitorum brevis.
Axon reflex
Scratch skin vasoconstricMon (white) oedema (red) surrounding vasodilation (flare)
abnormal in lesions distal to the ganglion.
Autonomic symptoms
Postural hypotension
Valsalva maneuvere (blood pressure, heart rate changes)
Carotid massage
Noadrenaline test (should cause increase in BP demonstrates supersensitivity)
Atropine tests (should cause increase in heart rate)
Sweating / TC response curve
Pupillary function to

Atropine dilaMon (blocking parasympatheMc)

Cocaine dilaMon (acMvate Adrenergic receptor)

55

Topic III/ 23 Neuropathies in diabetes mellitus

General
The condition is uncommon in childhood, and increases with age. Poor control over diabetes is related to
peripheral nerve damage, which is more common in type insulin-dependent patients.
Pathomechanism
Damage occurs from either metabolic disturbance with sorbitol and fructose accumulation in axons or Szhwann
cells or an occlusion of nutrient vessels supplying nerves (vasa vasorum). Neurological complications correlate
with levels of glycosylated haemoglobin A1C.

Classification
Polyneuropathy (in 30% of diabetics, only 10%
symptomatic)

Autonomic neuropathy

Affects the lower limbs, distally,

Ataxia if large fibre involvement, anaesthesia if small
fibre involvement
Reflexes are reduced earlier.
In most patients with polyneuropathy, some degree of
autonomic disturbance is present. Occasionally this

56

predominates
Pupil abnormalities
Loss of sweating
Orthostativ hypotension
Resting tachycardia
Gastroparesis and diarrhea
Hypotonic dilated bladder
Impotence
Assymmetric neuropathy
Pain, sensory loss and wasting of quadriceps. Loss of
knee jerk. Much less common than polyneuropathy.
Good functional recovery.
Oculomotor palsy, usually painless. May occur with
papillary sparing, which helps to differentiate from
th
th
aneurismal cause. The 6 and 7 cranial nerves may
also be involved in diabetes. Complete recovery.

Diabetic amyotropy

Cranial nerve palsy

Treatment
Improved diabetic control is essential. Carbamazepine, antidepressants or -adrenergic blockers help control
the pain. Drugs which reduces aldol reductase and halt accumulation of sorbitol and fructose ar beeing
investigated. Prognosis for much better for asymmetric neuropathies, rather than symmetric.
Topic III/ 24 Inherited neuropathies (Charcot-Marie, Dejerine-Sottas, Refsum)
General
HSMN, or Hereditary Motor Sensory Neuropathy, is a group of genetically founded diseases. Common for all of
them is distal wasting of the lower limbs. Once wasting of the legs is severe they resemble inverted
champagne bottle.
Disease
HMSN I
CharcotMarie-Tooth

Inheritance
AD or X-linked
Most common
HMSN 1:2500
Chr.no.17

Clinical features
Onset under 30
Pes cavus very common
Hammer toes
Ataxia
Tremor
Initially involving legs,
progresses if upper limbs
involves

Pathology
Demyelinating / remyelinating with
hypertrophy (onion bulb formation), adult
type, AD

HMSN II

AD
Chr.unknown
AR
Chr.no.17

Onset above 30
No foot deformities
CSF protein Onset in
childhood
optic atrophy retinits
pigmentosa
deafness
spastic paraparesis

Axonal loss

AR, named after

Initially (late childhood)

Is neurological disease that results in the

HMSN III
Dejerine - Sottas
disease

Refsum disease,

57

Demyelination, therefore decreased

conduction velocity with CSF protein
due to hypertrophied nerve roots.
Onion bulb formation.

or Heredopathia
atactica
polyneuritiformis

Norwegian
neurologist
Sigvald
Bernhard
Refsum (19071991)

Later

Retinitis pigmentosa,
or night blindness
Anosmia

malformation of myelin sheaths

(leukodystrophy) around nerve cells. It is a
peroxisomal disorder.

Ataxia
Scaly skin
(ichthyosis),
Hypacusis
Cataracts
Peripheral
neuropathy

Treatment
Avoid foods that contain phytanic acid,
including dairy products; beef and lamb;
and fatty fish such as tuna, cod, and
haddock. Plasmapheresis can prevent the
buildup of phytanic acid.

58

Topic III/ 25 Low back pain, and cervical disk disease

Pathogenesis of low back pain
Injury or trauma to the back (most
common)
Nerve or muscle irritation
Bone lesions.
Degenerative conditions such as arthritis
or disc disease, osteoporosis or other
bone diseases
Viral infections
Irritation to joints and discs
Congenital abnormalities in the spine

Obesity
Smoking
Weight gain during pregnancy
Stress
Poor physical condition
Posture inappropriate for the activity being
performed
Poor sleeping position also may contribute to low
back pain
Buildup of scar tissue from repeated injuries
eventually weakens the back and can lead to
more serious injury

a. Normal
b. Bulging disk
c. Focal bulge or protrusion.
The nucleus material
remains within the
outermost fibres of the
annulus fibrosus

Lumbar disc prolapse

Aetiology Trauma, heavy lifting
Old age disc degeneration
Location

L5-L5, L5-S1

Clinical

Lateral disc herniations usually compress the nerve

root exiting through the foramen below the affected
level. Eg. an L3/4 disc lesion will compress L4 root.

Diagnosis

Xray diminished disc space, spondylolithis,

exclusion of tumour
CT disc protrusion, joint hypertrophy, spinal canal diameter
MRI the best method.
59

d. Prolapse or
extrusion. The
nucleus material has
penetrated the
annulus fibrosus but
is contained in front
of the posterior
longitudinal
ligament.
e. Sequester or free
fragment.

Symptoms of lumbar disc prolapse

Lateral disc protrusion

Mechanical signs

Leg pain in the distribution of the affected root which extends

below the mid-calf. Coughing, sneezing or straining aggrevates
the pain.
Paraesthesia in the affected nerve root is also common
Restricted spinal movements
Scoliosis
Normal lumbar lordosis is lost
Lasegue sign (40-90) Crossed/inverted
Huftebeugung test

Neurological deficit

Central disc protrusion

Cauda equine syndrome

Usually bilateral , with one side more involved than the other
Leg pain and paraesthesio extending back on thighs, pain may
disappear with onset of paralysis
Sphincter paralysis: sensaMon and control. ConsMpaMon and
bladder problems tend to occur late.

Treatment
Analgesia, plaster, firm mattress, avoid lifting heavy weights or surgery, if:
1. Unremitting leg pain despite conservative treatment
2. Recurrent attaks
3. Development of neurological deficit
Beware that central disc protrusion may cause the neurosurgical emergency: compression of cauda equina,
that requires urgent surgical management as soon as possible to minimize neurological damage.

60

Cervical disc herniation

Etiology: Occurs most often in young patients, related to a sudden twist or injury to the neck.
Symptoms: Conscious patient: neck pain, and radicular arm pain, increased by head movements, paresthesia,
lateral herniation is more common radicular decit, central herniaMon is rare, and leading to myelopathy
(LMN at the same level, UMN below) Comatose patient: no symptoms

Neck tenderness, paraspinal swelling or a gap between spinous processes may indicate rupture of an
interspinous ligament.

Painless urinary retention or priapism (persistant erection)

Neurogenic paradoxical ventilation (indrawing of the chest during inspiration due to absent intercostal
function) may occur with cervical cord damage.

Lesion: The protrusion most often occurs posterolaterally at the C5/C5 or C6/C7 level, causing a rediculopathy
(spinal nerve root damage) rather than a myelopathy (spinal nerve damage).
C5:
biceps, deltoid, lateral arm sensory, biceps reflex
C6:
biceps, thumb, biceps reflex
C7:
triceps, finger extensor, triceps reflex
Diagnosis: Sagittal T1 weighted MRI or CT scan with intratechal contrast clearly outline the protruded disc.
Treatment: At impact, it is of essential importance to stabilize the involved level of injury to avoid exaberation
or precipitation of spinal cord injuries. There is a risk for this because bony or ligamentous damage may
accompany the spinal cord damage. Further management is surgery (discectomy) or conservative.

61

Topic III/ 26 Craniocervical developmental malformations

Arnold chiari malformation
Type I cerebellar tonsils slides below the foramen
magnum

th

Type II cerebellar vermis, medulla and 4 ventricle

slide below the foramen magnum

Type III meningomyelocele (cerebellum, medulla)

protruding between the cranium and cervical bones
Associated conditions
1. Syringomyelia (spinal cord)
2. Haydromyelia (spinal cord)
3. Hydrocephalus
4. Type II is associated with many abnormalities in the CNS
Clinical
Infant

Childhood

Adult

Respiratory difficulties

Gait ataxia

Lower cranial nerve

palsies

Syringomyelia
dissociated sensory loss,
spastic quadriparesis

Occipital headache with

coughing / straining

Nystagmus downbeat
or rotatory
Ataxia

Nystagmus

Retrocollis (neck
extension)

Spastic quadriparesis

Spasticity (rubrospinal
tract)

Progression to Bulbar
symptoms (respiratory
difficulties, lower cranial
nerve palsies)

Diagnosis
MRI T1 cerebellar ectopia with or without syringomyelia
Xray skull platybasia, fusion of cervical vertebrae, lumbar spina bida
Management
Ventriculoperitoneal shunt

Posterior fossa decompression

62

Dandy walker syndrome

Etiology
Rare developmental anomaly which, in 65% of cases is associated with other anomalies.
Clinical
Investigations
Management
Prognosis

Infancy: hydrocephalus and a prominent occiput

Childhood: Signs of cerebellar dysfunction with or without signs of hydrocephalus
Skull X-ray and CT-scan
Excision of cyst membrane or cystoperitoneal shunt
Marked neurological impairment prior to treatment carries a poor outlook. In less impaired
patients, the prognosis relates more to the presence of other developmental anomalies.
rd

1. Dilatation of lateral and 3

ventricles
2. Widely separated, hypoplastic
cerebellar ventricles
3. Enlarged posterior fossa with high
tentorium verebelli and transverse
sinuses
th
4. Cystic dilatation of the 4 ventricle
- usually related to congenital
absence of the foramina of Luschka
and Magendie
5. Thin transparent membrane
containing ependymal cells and
occasionally cerebellar tissue

Syringomyelia
Syringobulbia the cavity extends into the brain stem
Symptoms: sensory loss in the upper extremities with no motor deficiency.

63

Topic III/27 Malformation of the spine and spinal cord

Etiology
Classification

Diagnosis
Management

2/1000 births in Britain, geographical variations. Familiar incidence and teratogens

(e.g. Na-valproate) also have a role.
1) Myelomeningocele neurological signs
Spinal roots + spinal cord, protrude through the bony defect and lie within
the meninges lined cyst.
Myelodysplasia ruptured meningeal covering exposed to air, leakage of
CSF
2) Meningocele rarely neurological signs
Cystic CSF filled cavity, no neural tissue
Far less frequent than myelomeningocele and is rarely associtated with other
congenital anomalies.
3) Spina bifida oculata (5-10% of population)
Only a bone deficit, often cutnaoues abnormalities, lipoma may be seen
within the defect. Those who also have a lumbosacral cutaneous abnormality
however (tuft of hair, dimple, sinus or port wine stain have a high incidence
of
of related underlying defects: diastomatomyelia, lipoma or dermoid cyst.

US / MRI
Antenatal diagnosis: AFP, US
Surgical correction (excision, replacement, etc)
Cord tethering: conus medularis is tethered by the filum terminale below L1
Back pain, neurological deficit develop as cord stretched by faster
growing veterbral column
Diastatomatoyelia: congenital spinal cords splitting by bony/cartilage/fibrous spur.
Mostly in the upper lumbar area. Investigation: MRI, CT.
treatment: divide the tethered filum, remove the spur.

64

Topic III/ 28 Symptoms of the disorder of spinal cord

Sensory pathway lesions
Dorsal column (medial lemniscus)

Tracts: cuneatus, gracile (Goll, Burdach nuclei in the

brain stem)
Ipsilateral sensory loss (touch, proprioception, 2 point
discrimination, vibration)

Spinothalamic tract (anterolateral funiculus)

Tracts: Lateral spinothalamic tract (it sends pain fibre to

the RF too)
Contralateral loss of pain, TC
Ventral spinothalamic tract
Contralateral loss of crude touch

Dorsal spinocerebellar (proprio / extro - ception)

Ipsilateral leg dystaxia

Ventral spinocerebellar

Contralateral leg dystaxia

65

Lesions
1) Spinal ganglion lesions
(e.g. herpes zoster)

This will result in dermatome

involvement

2) Posterior roots lesion

The corresponding dermatome

becomes insensitive
Reflex arc is interrupted

3) Syndrome of posterior
tracts (prolapsed disc )

Posterior column

Proprioception loss
(position, vibration, 2
points discrimination)

Astereognosis
(recognition by touch)

Rombergs sign (ataxia

with closed eyes)
Increased sensitivity to pain
(substantia gelatinosa)
4) Syndrome of Posterior
horn

Pain & TC sensory loss (ipsilateral)

5) Central canal
compression (grey
matter)

All pathway crossing through the

Point are affected (anterior horn
and in front of the canal)

6) Severe combined
degeneration (posterior
tracts and corticspinal
tracts)

7) Syndrome of anterior
horns

pain & TC sensory loss

(bilateral on the that
level)

flaccid paralysis is present

if both sides are involved

This is caused by B12 deficiency

Pyramidal tract lesion

(spastic paraparesis)

Ataxia + Romberg positive

Increased tendon reflexes

Positive Babinsky

This is caused by poliomyelitis

Flaccid paralysis of the

corresponding muscles

66

8) Amyotrophic lateral
sclerosis

Anterior horn and pyramidal tract

damage
Pyramidal tract involvement
spastic paralysis
Anterior horn involvement accid
paralysis

9) Progressive spastic
spinal paralysis

The disappearance of the neurons of

the motor cortex lead to
degeneration of the corticospinal
tract only
Spastic paraparesis commonly
develops

10) Syndrome of anterior

and posterior roots and
peripheral nerves

This is called neural muscular

atrophy (hereditary)
Flaccid paresis, paresthesias, pain

11) Friedreichs ataxia

Associated with Diabetes mellitus

An autosomal dominant disease

12) Brown Sequard

syndrome (hemisection)

Dorsal column
Lateral spinothalamic
Ventral spinothalamic
Dorsal spinocerebellar
Ventral spinocerebellar
Hypothalamospinal
Lateral corticospinal
Ventral corticospinal
Ventral horn
Dorsal horn
areflexia

67

ispailateral loss of propriocepMon

contralateral Pain, TC
contralateral crude touch
ipsilateral leg ataxia
contralateral leg ataxia
horner syndrome
ipsilateral spasMc paralysis + babinsky
minor contralateral weakness
ipsilateral accid paralysis
ipsilateral dermatome anaesthesia &

13) Complete transection of

the spinal cord

The sudden interruption is called

spinal shock.
There is complete flaccid paralysis &
loss of all sensory modalities
Bladder, rectum and sexual control
are abolished
C1-C3 lethal
C4-C5 quadriplegia
Below T1 paraplegia
Above C5 breathing muscle paralysis

14) Syndrome of epiconus

(L4-S2)

Conus involvement (sacral segments)

15) Conus medullaris (C3Coccyx)

16) Syndrome of the cauda

equina (without the
conus)

17) Syringomyelia

LMN signs (flaccid paralysis)

dermatome sensory deficit

(e.g. saddle anaesthesia)

increased reflex (may

disappear later)

late bladder involvement

paralyitc bladder, faecal
retention, impotence

Sacral parasympathetic
nucleus (paralytic bladder,
faecal retention, impotence)

Saddle anaesthesia (S2-S5)

Mild motor deficit

(weakness of the foot)

Detrusor paralysis, overflow

incontinence, faecal
retention, impotence

Flaccid paralysis, sensory

disturbances develop
commonly due to tumours

Saddle anaesthesia

Reflexes are lost

This is the result of central cavitation

of the cervical spinal canal
Anterior comissure and crossing
spinothalamic fibres are destroyed
bilateral pain, TC loss
Anterior horn involvement produces
Upper motor neuron symptoms
Lateral funiculus involvement
produces lower motor neuron
symptoms

68

Topic III/ 29 The motor neuron disease (ALS, progr. Bulbar palsy)
Motor neuron disease: a disease in which there is a progressive degeneration of motor neurons in the cortex
and in the anterior horns of the spinal cord, and degeneration of the somatic motor nuclei in the cranial nerves
within the brainstem.
Motor neuron diseases are synonym for anterior horn cell disease, characterized by
1. Muscle wasting, with no sensory changes
2. EMG shows signs of chronic partial denervation, with abnormal spontaneous activity in resting muscle
3. Motor conduction velocity is normal
4. There are histological changes in muscle biopsy
5. CPK may be elevated
Progression to death occurs within 5 years.
1) Frontal atrophy (precentral gyrus)
Frontal dementia

2) Pseduobulbar palsy (has to be biltaral)

3) Progressive bulbar palsy

4) Amyotrophic Lateral Sclerosis (ALS)

5) progressive muscular atrophy

Spinal muscular atrophy
Post polio syndrome
Anti-GM1 antibody
Porphyria, Lead poisoning

69

Classification
1. Frontal atrophy
2. Progressive bulbar & pseudobulbar palsy
3. Amyotrophic lateral sclerosis (ALS)
4. Progressive muscular atrophy (PMA)
Progressive bulbar & pseduobulbar palsy
A motor neuron disease in which deficits are restricted to or begin with bulbar dysfunction
Slurred speech (XII, XI) dysarthria (differentiate from aphasia), changes in timbre of the voice (X) and later
difficulty in swallowing (XI)
If the lower motor neuron is involved, atrophy and fasciculations of the tongue (XII) as well as diminished
elevation of the soft palate (IX) occur.
Progressive upper motor neuron involvement leads to diminished facial (VII) expression, with hyperactive jaw
jerk (VII), frontal release signs, hyperactive gag response (X) and clumsiness of tongue (X) movements without
atrophy.
Bulbar palsy (Lower motor neuron signs)
Damage of the bulbar cranial nerves and/or motor nuclei, and / or intramedullary fibres and/or lower cranial
nerves (VII, IX, X, XI, XII)
Signs: paresis, atrophy, fasciculations, diminished reflexes (you stimulate the gag reflex by touching the back of
the pharynx, this way you can exclude a suprabulbar palsy, which will have a preserved reflex arc)
Pseudobulbar/ suprabulbar palsy (upper motor neuron signs)
Bilateral damage of the corticobulbar tract, producing bulbar dysfunction (dysarthria, dysphagia, paresis of
tongue) without signs of lower motor neuron disorder.
It is usually caused by ischaemic disease bilaterally in the hemispheres (frontal white matter or internal capsule
(or in the brain stem (basis pontis). Multiple lacunar infarcts may result in some combination of pseudobulbar
palsy, gait ataxia, subcortical dementia, and incontinence (like in Binswangers disease)
Bulbar involvement predominates
The upper motor neurons are affected (bilateral involvement of corticobulbar tract)
ALS
The name is used synonymously with motor neuron disease

It is characterized by mixed picture of Upper Motor Neuron (UMN) & Lower Motor Neuron (LMN) signs in
the limbs.
o E.g. spastic tetraparesis with brisk reflexes in association with marked wasting and fasciculations.

Pathology: destruction of anterior horn (LMN), and pyramidal tract (UMN)

Lower motor neuron

Upper motor neuron

Paresis and clonus

Flaccidity paresis, No clonus

Spastic paresis, Clonus

Fasciculations

Fasciculations

Absent

Muscle atrophy

Muscle wasting

Absent

Reflexes

Hyporeflexia
Superficial reflex is unaffected
Plantar response is flexion

Distribution

Segmental distribution

Brisk reflexes
Superficial reflex: depressed / absent
Plantar response is extension
Whole limb involvement
Muscle groups are involved according to the
pyramidal distribution
Upper limb weakness extensor >flexor
Lower limb weakness flexor >extensor
Skilled movements are more affected.

70

Classical findings
1. Brisk jaw jerk
2. Dyasrthria
3. Dysphagia
4. Wasting & fasciculation of the tongue
5. Normal sensory examination
6. Brisk reflexes
Primary lateral sclerosis
A pure upper motor neuron disease, diagnosis is based on exclusion of the previous 3.

Diagnosis
EMG: signs of denervation in muscles supplied by more than 1 spinal region

ENG: normal

Exclusion of other causes; MRI exclude compression, Thyroid, Ca

Differential diagnosis
ALS
1.
2.
3.

Cervical spondylosis
Spinal tumours
Hyperthyroidism, hyperparathyroidism (wasted fasciculating muscles with
brisk reflexes)

PMA (Progressive
Muscular Atrophy)

1.
2.
3.
4.
5.
6.

spinal muscular atrophy

Post polio syndrome
Poliomyelitis
Multifocal motor neuropathy (anti GM1 antibody)
Acute intermittent porpyria (-ALA in the urine)
Lead neuropathy

Pseudobulbar palsy

1.
2.
3.

cerebrovascular disease
MS
Brainstem tumours.

Spinal muscular atrophy (SMA)

Progressive Symmetric Lower motor neuron signs (wasting weakness, fasciculations) with preserved tendon
reflexes. Lower motor neuron lesion, caused by anterior horn cell degeneration
A group of non treatable disease, progressive destruction of the anterior horns of the spinal cord
Type I: Werding Hoffman syndrome (acute infantile SMA)

Autosmal recessive, loss of anterior horn cells, anterior root thinning. Fibre atrophy in the peripheral nerve.
Atrophy of muscle fibres

Reduced fetal movements, contractures, wasting, fasciculations.

Motor developmental milestones are delayed. Death within 18 months

Type II: Kugeberg Welander syndrome

Autosomal recessive/dominant, proximal muscle weakness, slowly progressive death within 12 years.

Type III: Adult onset SMA

Autosomal recessive, dominant, X linked.

Resembles ALS

Juvenile bulbar palsy (Kenedy syndrome)

X linked, drooling & dysarthria, aspiration pneumonia

Pyramidal signs, survivors do not pass age 20.

71

Treatment
Riluzole (NMDA antagonist) increases survival by 6 months

Insulin like growth factor 1

Speech therapy

Percutaneous endoscope gastrotomy (for swallowing problems)

Physiotherapy

Full palliative care in the terminal stage

72

Topic III/ 30 Muscular dystrophies

This is a group of inherited myopathic disorders characterized by progressive muscle weakness and wasting.
There is no treatment.
General about muscular diseases
Neuromuscular disorders
1. Radiculopathies
2. Plexopathies
3. Mononeuropathies
4. Polyneuropathies
5. Motoneuron diseases
6. Disorders of the
neuromuscular junction
7. Myopathies

Types of myopathies
Hereditary muscle diseases
1. Muscle dystrophies
2. Muscle channelopathies
3. Mitochondrial myopathies
4. Metabolic myopathies
Acquired muscle diseases
1. Inflammatory myopathies
2. Endocrine and toxic
myopathies
3. Infectious muscle diseases

Muscle dystrophies
X- linked
1. Duchenne muscular dystrophy
2. Beckers muscular dystrophy
3. Emery- Dreifuss
Autosomal Dominant
1. Facio-scapulo-humeral
dystrophy
2. Scapuloperoneal
3. Myotonic dystrophy
(trinucleotide)
Autosomal Recessive
1. Limb-girdle dystrophies
2. Enzyme deficiency of glycolytic
& lipid metabolism

Symptoms of muscle disease

Muscle pain and fatigue; exercise intolerance
Proximal and symmetric weakness
Waddling gait; difficulty of rising from sitting, climbing stairs; Gowers sign
(http://www.youtube.com/watch?v=IpoT46EAuCU)
Hyperextension of the knee
Increased lordosis of the lumbar spine, scoliosis
Contractures, tight Achilles tendons
Myopathic face
Muscle atrophy; pseudohypertrophy
Myotonia
Tendon reflexes are normal or depressed

Diagnosis of muscle diseases

Creatinine kinase levels increased in many myopathies (sign of muscle fiber necrosis)
ENG / EMG: differentiation between neurogenic and myogenic weakness
Muscle biopsy: signs of muscle fiber abnormality, inflammation, immunostaining of muscle constituents
Genetic testing

Muscular dystrophies
Hereditary myopathies, characterized by progressive weakness and muscle atrophy
Genetic defect of proteins constituting the sarcolemma-associated cytoskeleton system

73

Duchenne muscular dystrophy

Cause: Deficiency of dystrophin (X- linked), resulting in progressive loss of muscle fibers (Beckers type: reduced
amount of dystrophin; more benign course)
Incidence: 1 in 3500 live births, occurs in boys, girls are carriers

Clinical features
Onset: 3-5 years
Initial symptoms: Difficulty getting up from deep position and climbing steps, waddling gait
Weakness most pronounced in limb-girdle muscles, trunk erectors; craniobulbar muscles are spared
Skeletal deformities
Cardiomyopathy
Inability to walk by 9-11 years
rd
Death occurs usually in the 3 decade, from respiratory insufficiency

Diagnosis
Demonstration of deletion in the dystrophin gene
Lack of immunostaining of dystrophin in muscle biopsy specimen

Duchenne

Normal
Treatment
Prednisone, death by the age of 30

Emery Dreyfus dystrophy

Childhood onset, elbow, neck contractures, cardiomyopathy, muscle biopsy is non specific.

74

Facioscapulohumeral dystrophy - AD
Prevalence: 1 in 20,000

Clinical features
Age of onset: infancy to middle age
Progressive muscular weakness and atrophy involving the face, scapular, proximal arm and peroneal
muscles myopathic face, winging of the scapula, inability to raise the arms, foot drop
Life span is not significantly affected

Myotonic dystrophy - AD
Prevalence: 1 in 8000
Cause: CTG repeat expansion in a gene on chr. 19 AD inheritance, with anticipation

Multisystemic disease
Myotonia: hyperexcitability of muscle membrane inability of quick muscle relaxation
Progressive muscular weakness and wasting, most prominent in cranial (facial paresis) and distal muscles
Cataracts, frontal balding, testicular atrophy (gynaecomastia), bronchoectasia
Cardiac abnormalities, mental retardation

Diagnosis
CPK is moderately elevated
ECG: bradycardia
EMG: myotonia (wanin in the amplitude & frequency of motor uit potentials)

Treatment
Pacemaker, DM, cataract
Medical; Na channel blockers (phenytoin, quinine, procainamide)

Limb-girdle dystrophies - AR
Causes: 1) Sarcoglycanopathies (comprise about 10% of autosomal recessive limb-girdle dystrophies; , , ,
sarcoglycans), 2) Calpain deficiency, 3) Caveolin deficiency, 4) Dysferlin deficiency etc.
Sarcoglycanopathies
Clinical presentation:

Age of onset and severity is heterogeneous, usually starts between 2 and 20 years

Clinically often indistinguishable from Duchenne-dystrophy

No cardiac involvement

Diagnosis:

Normal dystrophin immunostaining, abnormal immunostaining with sarcoglycans

Genetic examination, where available

75

Topic III/ 31 Myositis and myopathies

General about muscular diseases
Neuromuscular disorders
8. Radiculopathies
9. Plexopathies
10. Mononeuropathies
11. Polyneuropathies
12. Motoneuron diseases
13. Disorders of the
neuromuscular junction
14. Myopathies

Types of myopathies
Hereditary muscle diseases
5. Muscle dystrophies
6. Muscle channelopathies
7. Mitochondrial myopathies
8. Metabolic myopathies
Acquired muscle diseases
4. Inflammatory myopathies
5. Endocrine and toxic
myopathies
6. Infectious muscle diseases

Inflammatory muscle diseases

1. Dermatomyositis
2. Polymyositis
3. Inclusion body myositis
4. Other systemic autoimmun
diseases (SLE, Sjgren sy. etc.)

Inflammatory muscle disease/ Myositis

Dermatomyositis
Humorally mediated autoimmune disease affecting the muscles and
skin (microangiopathy)
Symptoms progress over weeks, months
Rash on the face, neck
Periorbital oedema
Pain and weakness of proximal limb muscles, neck flexors
Dysphagia
Cardiac abnormalities, interstitial lung disease
Often paraneoplastic

Polymyositis
Cell-mediated immune response against muscle fibers
Symptoms are similar to DM, no skin involvement
Less often paraneoplastic than DM

Diagnosis / therapy of DM, PM

Blood CK levels are elevated
EMG: myogenic findings
Muscle biopsy: inflammation
DM: perivascular infiltration, mainly in the perimysium
PM: endomysial inflammation

Therapy
Immunosuppression, long-term treatment with corticosteroids (1 mg/day)
Dermatomyositis

Polymyositis

Inclusion body myositis

Clinical features

Proximal weakness

Proximal Weakness

Neurophysiology
Pathology

Myopathic

Myopathic

Axial and asymmetric distal

weakness
Mixed neurogenic/ myopathic

Necrosis, secondary inflammatory

infiltrate, perifasicular atrophy of
muscle fibers

Necrosis, inflammatory infiltrate, T

cell mediated necrosis; invasion of
healthy muscle fibers

Therapy
Associations

Steroids, IV Ig

Steroids; usually with azathioprine

Necrosis, inflammatory cell

infiltrate. Vacuolation with
inclusion bodies and paired helical
filaments at EM
None proven benefit

Paraneoplastic in adults

Weakly paraneoplastic

Sjgrens etc.

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Muscle channelopathies
Na channelopathies
1. Hyperkalemic periodic
paralysis
2. Paramyotonia
3.

Cl channelopathies
1. Myotonia congenital
(Thomsen and Becker type)

Ca channelopathies
1. Malignant hyperthermia
2.

Hypokalemic periodic
paralysis

Potassium aggrevated
myotonia

Hyperkalaemic periodic paralysis

Voltage gated Na channel mutation.
The disease develops by the age of 15, chronic proximal myopathy 2 hours after exercise after fasting and
during (insulin K)
Treatment: Ca-gluconate or salbutamol
Prophylaxis: thiazide diuretics or acetazoleamide

Myotonia congenital
Mutation in the muscle Cl gene - Autosomal dominant form: Thomsen, autosomal recessive form: Becker
Symptoms
Myotonia (hyperexcitability of the muscle membrane): muscle stiffness and abnormal muscle relaxation,
warm-up phenomenon
Hypertrophied muscles
Therapy: phenytoin, mexiletin
Hypokalaemic periodic paralysis
L-Calcium channel abnormalities
At the age of 20, generlized weakness develops after a heavy carbohydrate meal or after a period of rest
following strenuous exertion.
Serum K level < 3mmol/L.
Treatment with KCl,
Differential diagnosis: thyrotoxicosis.

Endocrine and toxic myopathies

Toxic myopathies
Drugs aimed at reducing blood lipid levels:
statins, clofibrate
Corticosteroids
Alcohol
Heroin

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Endocrine myopathies
Thyreotoxic myopathy: shoulder & pelvis brisk
reflexes, wasting
Hypothyreodism: pelvis & shoulder cramps
Hyperparathyreodism
Adrenal insufficiency: proximal weakness
Hypokalemia
Acromegally: proximal weakness

Metabolic myopathies

McArdles myopathy
Phosphorylase deficiency in the muscle
Exercise induce pain & muscle hardening unable to relax
Myoglobinuria
Diagnosis: Normal serum lactate after exercise + No phosphorylase activity in biopsy
Treatment: Oral fructose, Warm ups before exercise
Phosphofructokinase deficiency
Lactate dehydrogenase deficient
Carnitine palmityl trasnferase deficiency

78

Topic III/ 32 Primary headache syndromes

Definition: pain or discomfort between the orbits and occiput, arising from pain sensitive structures
Intracranial pain sensitive structures
Anterior fossa
Posterior fossa
Middle fossa
Innervated by IXth and
st
Innervated by the 1
Xth cranial nerves and
nd
the upper cervical
and 2 branch of Vth
nerves
cranial nerve
Pain referred to
forehead and
temporal regions

Included among the pain sensitive structures are

1)
2)
3)
4)

Pain referred to
Suboccipital and upper
cervical regions (ipsi- or
bilateral)

Extracranial pain sensitive structures

1) Scalp vessels & muscles
2) Orbital contents
3) Mucous membranes of nasal, paranasal
spaces
4) External, middle ear
5) Teeth, gums

Venous sinuses
Cortical veins
Basal arteries
Dura of anterior (V), middle (V), posterior
fossae (IX, X)

Classification
Recurrent episodic headache

1)
2)
3)
4)

Migraine
Cluster headache
Trigeminal neuralgia
Benign exertional headache

Chronic daily headache

1) Analgaesic overuse
2) Postherpetic neuralgia
3) Post traumatic headache

Subacute onset

1)
2)
3)
4)

Subdural haematoma (bridging veins)

Intracranial tumour / abscess
Chronic meningitis
Giant cell arteritis

Acute onset headache

1)
2)
3)
4)
5)
6)

Subarachnoid haemorrhage
Cerebral haemorrhage
Meningitis
Acute hydrocephalus
Hypertensive crisis
Acute glaucoma

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Primary headaches

1.Tension type headache

This is the most common type of headache, characterized by diffuse, dull, band like headache, worse by
touching the scalp, aggravated by noise.
Duration is for hours days (chronic), becoming worst towards the end of the day.
Mechanism: increased muscular tone.
Treatment: psychological stress, benzodiazepines, anMdepressants.

2.Migraine
Definition: a common (10% of the population, more common in ), often familial disorder characterized by
unilateral throbbing headache.
Types of migraine:
1. Common migraine (Migraine without aura)
Benign, periodic, pulsating headache (2-72Hours)
aggravated by physical activity
Accompanied by nausea, vomiting, photophobia, phonophobia
2. Classic migraine (Migraine with aura )
The headache is preceded by neurological symptoms (aura)
Aura: C shape scotoma, sensory, motor disturbances
Duration:
20-40min
Subtypes:
a. Basilar migraine
Disturbances in the brain stem function (vertigo, dysarthria, diplopia)
may last for 5 days.
b. Hemiplegic migraine
Aura of unilateral paralysis (misdiagnosed as stroke), recovery is a rule!
c. Ophthalmoplegic migraine
Extraocular nerve palsies (III mainly), caused by dilatation of the internal carotid artery with
stretching of the III or IV cranial nerves within the cavernous sinus
Pathogenesis
There are 3 mechanisms:
1. Vasomotor component
Cortical hypoperfusion that begins in the visual cortex (occipital)
The hypoperfusion localization spreads anteriorly in a wave like fashion irrespective of the anatomy of
the blood supply
The developing focal ischaemia induces symptoms
2. Serotonergic projections & dorsal raphe (reducing blood flow in peri-vascular inflammation)
Nucleus raphe has many serotoninergic projection to cerebral arteries, visual centres,
Prophylaxis of migraine is by 5-HT1D agonist (Sumatriptan)
Aborting migraine is by 5-HT1A agonist (Dehydroergotamine)
3. Trigeminal vascular system
Trigeminal nucleus of the medulla (pain processing centre for head & face region)
There is a release of substance P, and Calcitonin Gene Related Peptide
There is a genetic predisposition for this mechanism

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Precipitating factors
Dietary: alcohol, chocolate, cheese (tyramine)
Oestrogen: premenstrual, contraceptives
Stress, physical fatigue, exercise, sleep deprivation,
Diagnosis history
Differential diagnosis
Partial (focal epilepsy)
Aneurysm compressing the III cranial nerve
TIA
Arteriovenous malformations
Hypoglycaemia
Management
Acute attack
Analgesics (aspirin)
5-HT1 agonist (Sumatriptan) extracranial vessel vasoconstricMon
ergotamine extracranial vessel vasoconstricMon
methylprednisolone (for refractory cases)
Prophylaxis
5HT2 antagonist (pizotifen, methylsergide)
blockers (propranolol)
Ca channel blockers, antidepressants, anticonvulsants
Cluster headache (Histamine cephalgia)
Definition: most common in middle aged man, characterized by severe unilateral pain around one eye
(conjunctival injections, lacrimation, rhinorrhoea, transient horners syndrome)
Duration: 10minutes 2 hours
Pathogenesis: serum histamine rise during the attack (histamine cephalgia)
Treatment:
antihistamines do not work !
Sumatriptan or prednisolone

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Topic III/ 33 The neuralgias

1) Trigeminal neuroalgia
The trigeminal nerve supplies sensation to the skin of the face and anterior half of the head. Its motor part
innervates the masseter and pterygoid masticatory muscles.

Trigeminal neuralgia (paroxysmal facial pain, Tic Douloureux) is a several minutes episode of severe pain
throughout the distribution of the Trigeminal nerve, which occurs sporadically over several weeks. It is common
in middle aged women.
The pain can be triggered by stimulation of several places (lips, tongue, chewing, tooth brushing, speaking)
Aetiology:
Idiopathic
Demyelinative plaque at the root entry zone of the V nerve
Tumour (lying in the pontocerebellar angle)
Tortuous blood vessel in the posterior fossa arising from the superior cerebellar artery curl around the
unmyelinated part of the nerve (causing irritative lesion of the nerve)
Herpes zoster
Diagnosis: clinical criteria (which are based on the description above)

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Differential diagnosis
1) Diseases of Jaw, teeth, sinuses
2) Glaucoma / iritis may radiate to the forehead
3) Charlins syndrome (sever pain in the inner corner of an eye caused by irritation of the ciliary
ganglion)
4) Gradenigos syndrome (refers to pain in the area of the frontal branch of the V nerve,
associated with paresis of the IV nerve and is attributed to inflammation of the pneumatic
cells in the petrous bone)
5) Bing Horton syndrome (erythroprosoplegia) there is reddening of the ipsilateral half of the
face, pain occurs during sleep, usually accompanied by Horners syndrome
6) Aneurysm of the internal carotid.
7) Facial neuralgia
8) Cephalic neuralgia
Treatment:
Carbamazepine
Surgery
i. Percutaneous retrograde rhizotomy (nerve root incision)
ii. Injection of glycerol in the Meckels cave
(the part of dura which holds the Gassers ganglion)
iii. Microvascular decompression (suboccipital craniotomy)
2) Glossopharyngeal neuralgia
More common in males.
Pain is in the tonsillar area, posterior pharynx, base of tongue with radiation to the ear.
Triggered by talking, swallowing
Accompanied by bradycardia, syncope (stimulation of vagal nuclei)
Treatment: carbamazepine, phenytoin, microvascular decompression.
3) Post herpetic neuralgia
This occurs following zoster reactivation, incidence rises with age.
Constatnt, sever, burning pain in the affected dermatome (V, or spinal)
May persist for months years
Treatment: carbamazepine, phenytoin, tricyclics

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Topic III/ 34 The physiological sleep and the sleep disorders

Physiology of sleep
Sleep results from activity in certain sleep producing areas of the brain rather than from reduced sensory input
to the cerebral cortex. Stimulation of these areas causes sleep; damage results in states of persistent
wakefulness.
Stages of sleep
The stages are defined on basis of polysomnography (EEG, EOG, EMG)
Two main stages of sleep are recognized
Rapid Eye Movement (REM) sleep

Non-REM sleep

Rapid conjugate eye movement

Yes

No

Fluctuation of temperature, BP,

heart rate and respiration

Yes

No

Muscle twitching

Yes

No

Presence of dreams

Yes

No

Originates in:

Pontine reticular formation

Midline pontine and medullary

nuclei (raphe nuclei)

Mediated by:

Noradrenaline

Serotonin

*In view of the important role of noradrenaline and serotonin in sleep, it is understandable that drugs may
affect the duration and/or content of sleep.
Physiological changes during sleep
Blood pressure & heart rate

Respiratory rate
Endocrine

Neurochemistry of sleep
Neuroantomical basis of
sleep

Decrease in blood pressure & heart rate during NREM

Burst of eye movements and variable blood pressure & heart rate
during REM

More regular during NREM, irregular during REM,

pCO2 levels are higher.

Increased Growth hormone, prolactin, melatonin

During sleep LH in puberty, LH in mature woman

Inhibition of TSH, ACTH

Melatonin levels are persistent in patients kept awake the whole night

Attenuation thermoregulatory capacity

Serotonin, prostaglandin D2 (sleep promotion)

Catecholamines (wakefulness)

Anterior hypothalamus (sleep centre)

Posterior hypothalamus (wake centre)

Medullary reticular formation of the thalamus, basal forebrain

(generation f sleep)

Brainstem reticular formation, subthalamus (wakefulness)

Suprachiasmatic nuclei of hypothalamus are the central pacemaker

Lesions of the dorsal pons

produce REM sleep
Circadian rhythm

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Disorders of sleep
Classification
1) Dyssomnias:
Disturbance of normal sleep or rhythm pattern.
2) Parasomnias
Any dysfunction associated with sleep
3) Disorders associated with medical / psychiatric disorders
1) Insomnia
Definition: inadequate sleep, involving either falling asleep, maintaining sleep, awakening, or excessive sleep
despite adequate sleeping time.
Aetiology:
psychogenic factors
Altitude insomnia (Characterized by periodic breathing of cheyne stokes.
Treatment with acetazolemaide
Drugs, alcohol
2) Narcolepsy
Definition:
excessive day time sleepiness with involuntary daytime sleep episodes., disturbed nocturnal
sleep and cataplexy (sudden weakness or loss of muscle tone without loss of consciousness that is elicited by
emotion). The disorder is inherited.
Diagnosis:
Presence of the tetrad:
1) excessive day time somnolences, 2) cataplexy,
3) hypnogogig hallucination, 4) sleep paralysis.
Multiple sleep latency test (MSLT)
Documentation of abnormal REM
Treatment:
Stimulants (methylphenidate)
3) Sleep apnoea syndrome
Respiratory dysfunction during sleep. With increased risk of cardiovascular death
Aetiology: anatomical abnormalities, absence of respiratory effort (central sleep apnoea)

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4) Restless legs syndrome

This a dyssomnia, the patient reports an irresistible urge to move his leg when awake and inactive, especially
when lying in bed before sleep.
5) Nocturnal myoclonus
Limb kicks during sleep. treat with benzodiazepines
6) Parasomnias
A behavioural disturbances during sleep that are associated with bried or partial arousals but not with marked
sleep distruption.
Somnambulism (sleepwalking)
Sleep terrors
Sleep burxism (grinding of teeth)
Sleep enuresis
7) Sleep disorders associated with medical / psychiatric disorders
Psychiatric disorders:
These maybe with insomnolence of schizophrenia, depression.
Hypersomnolonece in depression.
Neurological disorders
Chronic pain (cervical spondylosis)
Dementia
Epilepsy
Fatal familial insomnia (bilateral degeneration of anterior dorsomedial nuclei of
Thalamus)
8) Circadian rhythm sleep disorders
Jet lag
Shift work sleep disorder
Delayed sleep phase syndrome (always sleep a little later than needed)
Non 24H sleep wake disorder
Process of evaluation
1) Patient`s sleep record
2) Polysomnogram

Sleep awake pattern for 2 weeks

Respiratory effort, air flow, O2 saturation

Anterior tibialis EMG

ECG

3) Multiple sleep latency test (MSLT)

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87

Topic III/ 35 Genetic background of muscle disorders

X linked:

Autosomal dominant:

1) Duchenne
2) Beckers
3) Emery Drefiuss

1) Facio-scapulo-humeral
Scapuloperoneal
2) Myotonic dystrophy

Autosomal recessive
1) Limb girdle dystrophy
2) All enzyme deficiency of
glycolysis & lipid
metabolism

Dystrophin gene: Duchene, Beckers

Myotonin protein kinase (trinucleotide repeat mutation):
dystrophic myotony
McArdles syndrome

skeletal muscle glycogen phophorylase deficiency (myophosphorylase)

No degradation of the non reducing ends of the glycogen
Weakness, cramping of skeletal muscles after excersize
No rise in blood lactate during strenuous exercise

Phosphofructokinase deficiency
LDH deficiency
Carnitine palmityl trasnferase deficiency
Periodic paralysis
Hypokalaemic (Ca channel)
Hyperkalaemic (Na channel)
Mitochondrial myopathies

88

Topic III/ 36 Inborn metabolic disorders affecting the nervous system

Classification
1) Amino acid metabolism

mental retardation, seizures

Phenylketonuria

albinism

Homocystinuria

marfan like syndrome, cataract

Maple syrup disease

2) Purine metabolism

Lesch Nyhan syndrome

(hypoxanthine guanine
posphorybosil transferase)
Xantine oxidase deficiency

3) Pyrimidine metabolism

Xeroderma pigmentosum

4) Porphyrias (Lead poisoning,

different mitochondrial enzymatic
deficiencies)
5) Lipoprotein

Abetalipoproteinaemia
Tangier disease

6) Cu metabolism

Wilsons disease
Menkes kinky hair syndrome

7) Mitochondrial disorders

MELAS, MERRF, CPEO

8) Peroxisomal disorders

Infantile Refsums disease

Adrenoleukodystrophy (Krabbe,
Farber)

9) Storage diseases

Glycogen storage disease

(Pompes)
Cholesterol storage diseases
Lipofuccinosis
Mucopolysaccharidoses (Hurlers,
Hunters)
Sphingolipidoses (GM1, GM2,
Nieman pick, Gaucher,
Krabbes, Fabrys,
Metachromoatic leukodystropy)

10) Kernicterus

89

Topic III/ 37 Trinucleotid repeat diseases (Huntington chorea, fragile X, dystrophia myotonica)
Pathophysiology & introduction
There are at least 10 such neurological disorders.
The disease means that trinucleotide expand within a gene. The expansion may be in the

5` untranslated region

within the open reading frame (translated portion)

within the 3 untranslated region

within the introns

4 categories
1) Fragile X
There are 4 fragile X sites located on the long arm of the X chromosome.
And are associated with repeat of CGG or CCG.
The expansion prevents protein transcription.
---------------------CGG CGG CGG CGG CGG CGG CGG CGG CGG
it is more common in men, mental retardation, dysmorphism large ears,
broad forehead, testes grow large with age.

2) Huntingtons disease (Setesdalsrykkja eller arvelig Sanktveitsdans)

This is part of 6 degenerative diseases which are characterized
by CAG repeat expansion in the open reading frame.
(Huntington, kennedy syndrome, spinocerebellar ataxia)
The CAG repeat is translated into a polyglutamine (CAG) chain
which results in cross linking of the product protein. The nature
of the abnormal protein product interacts which neuronal group
specific intracellular product which leads to neurtoxicity in these groups.

90

3) Myotonic dystrophy
This disease belongs to the category of repeat expansion in the 3 untranslated region of the kinase gene. The
repeat is CTG.
The 3` untrasnlated region is responsible on the control over the rate of kinase protein expression. The repeat
expansion will lead to an alteration in the kinase levels. It also may later adjacent neighbouring genes.
4) Freidreichs ataxia
This category reflects the repeat expansion within the intron. The expansion results in inhibition of transcription
or disrupted RNA splicing. Which means decreased mRNA levels.

Clinical description of the diseases

1) Fragile X syndrome
See above.
It is more common in men, mental retardation, dysmorphism large ears, broad forehead, testes grow large
with age.
2) Huntingtons chorea (CAG = polyglutamine repeat)
An autosomal dominant. Degenerative brain disorder, with a frequency of 10:100,00. it is characterized by: 1)
chorea, 2) dementia, the disease lasts for 15 years, may be seen in both adults and children, but it is much more
common in 50 year olds.
The disease affects the striatum (caudate, putamen). Synthesis of GABA in the basal ganglia is decreased.
Clinical
The chorea is irregular, sudden jerks of the limbs or trunk.
Gait is disturbed (dancing like), and articulation is impaired
Memory is preserved until very late stages of the disease. depression, apathy, social withdrawal Irritability are
common. Delusions and obsessive compulsive disorder are seen. Schizophrenia may be the initial diagnosis.
Diagnosis
Blood test to detect the expansion of the CAG for more than 38 times. The more the repeats the earlier the
disease is expected to appear.
MR: atrophy of the caudate & putamen.
No Treatment

91

3) Myotonic dystrophy
It is the most common type of adult muscular dystrophy Incidence 10:100,000. an autosomal dominant disease,
CTG repeat on chromosome 19 (myotonin protein kinase)
Clinical
Hatchet faced appearance (temporalis, masseter, facial muscle atrophy)
Distal limbs, muscles of the neck are weakened. Extensor of wrist and foot are affected (drop foot / hand).
Speech problems, dsyphagia (palatal, pharyngeal muscles), respiratory muscle involvement leads to respiratory
insufficiency.
Cardiac disturbances are inevitable.
The patients intellect is impaired, hypersomnia, cataract, frontal baldness, insulin resistance, decreased bowel
motility.
Diagnosis
Mild elevation of CK
EMG: polyphasic waves, etc
Muscle biopsy: muscle atrophy of the type I fibres,
increased number of central nuclei
no necrosis & connective tissue (which is typical for other musclar dystrophies)
Treatment
usually no treatment is needed.
Phenytoin, quinine, procaineamide (antimyotonic drug)
Cardiac abnormalities should be addressed.

Spinocerebellar ataxia includes: 1) friedriechs ataxia, 2) ataxia telangiectasia

Difference between spasticity and rigidity
Spasticity

Rigidity

Lesion in upper motor neuron

Lesion in basal ganglia and connections

Increased tone more marked in flexors in arms and

extensor in legs

Increased tone equal in flexors and extensors

Increased tone most apparent early during movement

(clasp knife)

Increased tone apparent throughout range of

movement

Reflexes brisk with extensor plantars

Normal reflexes with flexor platnars

92

Topic III/38 Genetic background of dementias

Alzheimer disease:

Early onset:

Presenilin 2 (1, q) membrane protein

Presenilin 1 (14, q) membrane protein

Late onset
Apolipoproteine E4 (19)
Familial alzehimer

APP (autosomal dominant) causing elevation

in amyloid

Huntington

CAG repeat = poluglutamine myotonin protein

kinase

Familial CJD

PPr gene mutation

Gesterman straussler schenker

PPr gene mutation

Wilsons disease

Defective transmembrane Cu-ATPase

93