CASE 3

A 13year old female child presented with complaints of

 Abnormal movement of hands x3 years
 Difficulty in walking x 3 years
 Behavioural issues x 2 years
 Drooling of saliva X 2 years
 Fixed open mouth x 6 months
HOPI
Patient developed abnormal movements of the hands, noted 3 years back.

There was mild shaking movements but she was able to do her daily activity. Slowly
the movements have increased over last 6 months.

Presently she is having difficulty in her usual activities- putting buttons,

writing,eating with spoon.

 Difficulty in walking since last 3 years. She had mild swaying while walking. This
slowly increased, with decreased ability to balance herself while walking.

Behavioural issues since last 2 years. Increased aggressive behaviour, decreased

understanding, eventually loss of school for last 1 year.
Drooling of saliva since 2 years
 Opening of mouth since 6 months. There was tightness in the jaw, which
increased after which the patient had kept her mouth open. Patient was able to
eat slowly, and she was able to close her mouth intermittently and during sleep.
No h/o fever, headache, vomiting
No h/o skin rashes/lesions
No h/o any chronic drug intake
No h/o joint pain
No h/o feeding difficulty- difficulty in swallowing, no regurgitation of food
 No past history of jaundice, seizures, exanthematous skin lesion
 Birth history was normal. First born in a non consanguineous marriage
 No H/O similar illness in the family .
Pedigree tree

13 year 8month
 Development was normal. Attained all milestones according to age
 Immunized according to NIS till age.
GENERAL EXAMINATION
General examination- Vitals stable.
Pallor +
No Icterus, Cyanosis, Clubbing, Lymphadenopathy
Anthropometry- Severe underweight, Severe thinness
Head to toe: Open fixed mouth
Gait- Swaying +, wide base
Normal
SYSTEMIC EXAMINATION
CNS
• HMF-
• Oriented to time , place , person
• gait-unstable( swaying present) , not able to walk alone
• speech- slurred speech
• CN – normal
• Motor system-
• posture- tremors +, mouth open, upperlimbs and lower limbs in flexed position
• Bulk- b/l equal
• Tone-hypertonic in all limbs (leadpipe)
• Power ->3/5
• Reflex-hyporeflexia in knee, ankle, biceps, triceps. Planter – flexor
• Cerebellum- tremor present
• Sensory system – normal
• RS, CVS, ABD NORMAL
 Differential diagnosis
• Neuro Wilson disease
• Autoimmune encephalitis
• Post encephalitis sequelae
• Neurodegeneration with brain iron
accumulation disease
• Metachromatic leuckodystrophy
• SSPE
INVESTIGATIONS-
HB 11.6 TP 7.3

TC 4400 ALB 4.6

AST 23
N/L/E/M 30/62/2/4
ALT 14
PLT 143000
TB 0.8
PCV 35
DB 0.3
ALP 169
 MRI BRAIN- Bilateral symmetrical t2/FLAIR hyperintensity is seen from basal ganglia and
thalamus
SLIT LAMP EXAMINTION S/O KF RING
FIBROSCAN - Median stiffness- 9 kpa(< 10).
USG ABDOMEN- Mildly coarse hepatic echotexture with moderate
splenomegaly.
• S.CERULOPLASMIN- <3 (16-45)
• S.COPPER- 32.9 (80-155)
• U.copper
Neuro and Gastro opinion was sought.
Final diagnosis
• WILSON’S DISEASE WITH NEUROLOGICAL MANIFESTATION
ADVICE ON DISCHARGE

Tab PENICILLAMINE 250 MG 1-0-0 ONCE WEEKLY X 4 WEEK

TWICE WEEKLY X 4 WEEK

ALTERNATIVE DAY X 4 WEEKS PENICILLAMINE TO BE TAKEN IN EMPTY

STOMACH(BEFORE MEAL OR AFTER 2 HOUR OF
DAILY X 4 WEEKS FOOD)

TAB PENICILLAMINE 250 1-0-1 X 4 WEEK

TAB PENICILLAMINE 250 1-1-1 X to continue

TO CONTINUE
• T. Baclofen 5mg 1-2-1 x 1 week and increase gradually
• T. Trihexyphenidyl 2mg 1-0-0 x 4 days and increase gradually
• T. Zinconia 50 mg 1-1-1
• T. Pyridoxime 40 mg daily
• Occupational therapy, physiotherapy, speech therapy to be continued
• Copper restricted diet
• Screening for siblings for KF ring, serum ceruloplasmin and serum copper
• Do CBC, LFT, PT/INR , Urine routine weekly for 6 weeks
CASE 4
A 9 year old female child came with the complaints of
Generalized tiredness x 6 months
Difficulty in speech , writing , walking x 6 months
Tremors x 6 months
HOPI-
Difficulty in speaking noticed by parents x 6 months, gradually progressed .
Currently child is not able to speak with fluency .

Difficulty in walking since last 6 months.

She had mild swaying while walking. This slowly increased, with decreased
ability to balance herself while walking.. History of occasional falls present.

Child having mild trembling movemets but she was able to do her daily
activity. Slowly the movements have increased over last 6 months. Presently
having difficulty in writing and fine motor activities( dressing/undressing ,
drawing ) x 6 months
No h/o fever, headache, vomiting
No h/o skin rashes/lesions
No h/o any chronic drug intake
No h/o joint pain
No h/o feeding difficulty- difficulty in swallowing, no regurgitation of food
Past history-
• H/O Jaundice 3 years back, for which she was treated for 1 week and discharged.
• Birth history- Normal
• Family history-
No family h/o jaundice, abnormal movements, behavioural changes
PEDIGREE – 3rd degree consanguinous marriage
Development history- Attained all milestones at appropriate age.Currently not
going to school since 1 year due to present illness
Immunized according to NIS.

GENERAL EXAMINATION-
General examination- Vitals stable.
Pallor
No Icterus, Cyanosis, Clubbing, Lymphadenopathy
Anthropometry-
Weight-18.5kg (< 3P)
Height – 121 cm (3-10P)
BMI – 12 (severe thinness)
Head to Toe- Normal
SYSTEMIC EXAMINATION-
CNS
• HMF- Conscious , cooperative , oriented to time place person
• Gait- clumsy gait
• Speech- dysarthric speech
• Cranial nerve – normal
• Motor-
• bulk- normal
• Tone- Normal in all 4 limbs
• Power -5/5 in all limbs
• Reflex- 1+ in knee , ankle , biceps, triceps
• Plantar – flexor response
 • Sensory system – normal
• Cerebellar signs- Normal
• P/A
• Soft , nontender
• No HSM
• No free fluid
• CVS and RS - normal
DIFFERENTIAL DIAGNOSIS?
• Neuro Wilson disease
• Autoimmune encephalitis
• Post encephalitis sequelae
• Neurodegeneration with brain iron
accumulation disease
• Metachromatic leuckodystrophy
• SSPE
INVESTIGATIONS-

TP 6.8
ALBU 4.5 • PT-14.6
MIN
TB 0.8
• INR-1.21
DB 0.37 • S.creat-0.8
AST 33
ALT 16
ALP 180
GGT 12
MRI BRAIN WITH SPECTROSCOPY

B/L near symmetric T2/FLAIR hyperintensities T1 hypointensities involving basal

ganglia ,thalamus brainstem, b/l frontal parietotemporal cortical regions.No lactate peak on MR
spectroscopy . Findings are highly suggestive of a metabolic disease process. Possibility of
Wilsons disease need to be ruled out.

USG ABDOMEN –

• LIVER: The liver span is 9.1 cm, shows coarsened echotexture . There are no focal lesions. The
portal vein is normal, shows hepato petal flow. PSV is 18.5 cm/sec .

• BILIARY SYSTEM: The gall bladder is distended, and shows calcareous sludge within.
Nocalculi. Mild irregular wall thickening noted measuring 3.3 mm in maximum thickness. The
proximal CBD is normal. The distal CBD is obscured. The intra and extra hepatic bile ducts are
SLIT LAMP EXAMINATION- KF RING +

FIBROSCAN- Median stiffness- 13.6 kpa(< 10)

Urine copper(ICPMS)/24 hours- 179 mcg/24hours (<53)

Serum copper (ICPMS)- 44mcg/dl (74-130)

Serum ceruloplasmin- below 3 mg/dl (30-65)

Gastro and Neuro opinion sought

Final diagnosis
WILSON’S DISEASE WITH NEUROLOGICAL MANIFESTATION
ADVICE ON DISCHARGE
• T. Penicillamine 250 mg 1 1/2-0-1 1/2 once weekly x 4 week
• T. Baclofen 5mg 1-2-1 x to continue
• T. Trihexyphenidyl 2mg 1-0-0 to continue
• T. Zinconia 50 mg 1-1-1
• T. Pyridoxime 40 mg daily
• Occupational therapy, physiotherapy, speech therapy to be continued
• Wilsons diet
• Screening for siblings for kf ring, serum ceruloplasmin and serum copper
• Do CBC, LFT, INR, Urine routine weekly for 6 weeks
NEURO-WILSON
 The prevalence of the neurologic manifestations is a study by Machado et al. in decreasing
order as follows: dysarthria 91%, dystonia 69%, Parkinson's symptoms (rigidity 66%, resting
tremor 5%, bradykinesia 58%), cerebellar disturbances 28%, chorea 16%, and athetosis14%.

 The prevalence of cognitive impairment is rare with a frequency of 4.2%.

Reference
 The clinical manifestation of dystonia in WD is broad. It ranges from mild cases to severe
disease and could manifest as focal, segmental, multifocal, or generalized symptoms.

 Focal manifestation includes torticollis, blepharospasm, and risus sardonicus.

 Risus Sardonicus is the most characteristic presentation and manifests as a fixed smile
due to the dysfunction of the risorius muscle.

 Focal dystonia of the vocal cords and articulation muscle may produce dysphonia,
dysarthria, and dysphagia.
RISUS SARDONICUS
Putamen mainly involved with dystonic movements

Basal ganglia damage Failure of thalamocortical motor circuit to generate an

inhibitory signal in the cortical neurons Increased motor output increasing
activity of the direct pathway of the basal ganglia.

 Dystonia is not only a basal ganglia disease. It also has a cerebellar and cortical disease
component.

 At the early stage of the disease, the predominant location of symptoms is unilateral.

 As the disease progresses, it turns bilateral and often generalized

 Ataxia involves abnormalities of the posture, gait, dysdiadochokinesia, dysmetria, hypotonia,
oculomotor abnormalities, tremor, and speech disturbances.

FRONTAL LOBE
SYNDROME
 Cognitive changes

SUBCORTICAL
DEMENTIA
 Frontal lobe syndrome results from frontal lobe degeneration, which presents a disorder of the
executive function and behavior changes.

Subcortical dementia is characterized by memory loss, personality changes, mood disturbances,

and slowness of mentation.
Dysarthria is a motor speech disorder characterized by imprecise, slow, weak,
and uncoordinated speech.

All speech mechanism components may be affected in different manners, such

as features associated with articulation, phonation, prosody, respiration, and
resonance.

 Dysarthria is caused by multiple regions of the brain and hence a specific

pathophysiologic mechanism was not found for dysarthria.
 The mean levels of copper levels were higher in patients with seizures (35.87) vs. patients
without seizures (31.72)

 Penicillamine treatment pyridoxine deficieny decreased GABA lower the

seizure threshold.

 Direct toxicity of copper due to inhibition of membrane ATPase

 The presence of copper generates oxidative stress, which releases glutamate and pro-
inflammatory cytokines

 It is important to note that MRI findings with lesions in the frontal lob were the most
common findings in patients with seizures in WD
WD neurologic symptoms Possible therapeutic interventions
BTX, botulinum toxin; DBS, deep brain stimulation; GPi, globus
pallidus internus; STN, subthalamic nucleus; Vim, ventral
intermediate nucleus of the thalamus; WD, Wilson disease

1. Tremor Beta-blockers (propranolol)

Barbiturates (primidone)
Benzodiazepines (most commonly—clonazepam)
Anticholinergics (trihexyphenidyl or biperiden)
Presynaptic gamma-aminobutyric acid agonist (baclofen)
BTX injections
Neurosurgical treatment—Vim DBS or thalamotomy

2. Dystonia Anticholinergics (as in WD tremor treatment)

Presynaptic gamma-aminobutyric acid agonist (baclofen)
Benzodiazepines (as in WD tremor treatment)
Levodopa or dopamine agonists (e.g., ropinirole or pramipexole)
Dopamine depleting drugs
Antiepileptics drugs (m/c carbamazepine, oxcarbazepine or
gabapentin);
BTX injections
Neurosurgical treatment—DBS of GPi, pallidotomy or thalamotomy
3. Parkinsonism Levodopa
Dopamine receptors agonists
Neurosurgical treatment—DBS or neuroablative lesions of GPi or STN

4. Chorea Dopamine depletion agents (tetrabenazine)

5. Dysphagia Behavioral therapy

Dietary modifications
Stopping the drugs influencing arousal
Neuromuscular electrical stimulation
Tube feeding (percutaneous gastrostomy) if needed

6. Dysarthria Speech therapy

Augmentative communications devices if needed

7. Drooling Non-Pharmacological methods

Anticholinergics
Adrenergic alfa-2 receptor agonists
BTX (injection in parotid and submandibular glands)
THANKYOU