Case Based Discussion

Facilitator: Prof Minn Soe

Date: 17-12-2020

Nikitha Dalavai
BMS16091676
 Case -
A 52 year old man was admitted with 1-week history of difficulty using his right arm. His
family also reported that for 2 weeks his memory had been impared and that he had
been intermittently confused. Five years ago he was treated for Hodgkin’s disease
(stage 3B, nodular sclerosing type) with splenectomy, chemotherapy, and radiotherapy,
and he had recently completed an additional course of local irradiation to the neck
because of a local recurrence.

On examination, he was afebrile and appeared confused. Speech was fluent but
dysphasic, with paraphasic errors and neologisms. Testing of extraocular movements
revealed absent upgaze and sustained nystagmus on right lateral gaze. There was a
right hemiparesis involving arm more than leg or face and bilateral extensor plantar
responses. Limbs were ataxic and gait was staggering.
 Case Highlights
Hodgkin’s Disease - treated five years ago with, splenectomy, chemotherapy and
radiotherapy.

Hemiparesis - Right sided involving arm more than leg or face.

Dementia - memory impared for past 2 weeks and intermittent confusion.

 Provisional Diagnosis

Progressive multifocal leukoencephalopathy (PML) -

Is a demyelinating disease of the central nervous system (CNS) characterized by

widespread lesions due to infection of oligodendrocytes by JC virus, which is a human
polyomavirus (formerly known as papovavirus).

● PML occurs almost exclusively in patients with severe immune deficiency, most
commonly among patients with acquired immune deficiency syndrome (AIDS)
● People on chronic immunosuppressive medications including chemotherapy are also
at increased risk of PML, such as patients with transplants, Hodgkin's lymphoma,
multiple sclerosis, psoriasis, and other autoimmune diseases.
 Differential Diagnosis
● Creutzfeldt-Jakob Disease - generally does not preferentially occur in the
immunocompromised population like PML and does not show large lesions like those
shown in the CT scan of PML.
● Multiple sclerosis - early in the disease MS and PML may appear similar, but PML
progresses much more quickly. The breakdown of myelin in PML is commensurate with
the degree of immunocompromise.
● Multiple Cerebral emboli - seen in patients with underlying malignancy, can give
similar a clinical and CT scan picture similar to PML.
● HIV/AIDS encephalopathy - often diffuse white matter disease, with atrophy,
symmetric, spares the subcortical U-fibers, whereas PML consists of focal lesions have
a subcortical U-fiber distribution.
 Differentials CONT’D
● Posterior reversible encephalopathy syndrome (PRES) - differing clinical history as
patient is most often hypertensive, but can involve both grey and white matter
● Immunodeficiency-associated CNS lymphomas - usually enhance following
injection of contrast dye, whereas PML lesions do not enhance.
 Investigations
● Brain MRI -
○ Typically seen as multifocal, asymmetric periventricular and subcortical
involvement. There is little, or no mass effect or enhancement and the subcortical
U-fibers are commonly involved with a predilection for the parieto-occipital regions.
○ ≥1 T2/FLAIR hyperintense and T1 hypointense lesions involving the subcortical
and juxtacortical white matter, some may exhibit faint rim enhancement
● Brain CT -
○ Asymmetric focal zones of low attenuation involving the periventricular and
subcortical white matter.
● Cerebrospinal Fluid -
○ CSF JCV PCR (commercial or ultrasensitive/quantitative PCR) positive
● Brain Biopsy -
○ Is the definitive diagnostic test
○ Histopathology: demyelination, bizarre astrocytes, and oligodendroglial nuclear
inclusions
○ Tissue PCR for JCV positive
 Management
● Currently there is neither a specific prophylaxis for PML, nor an effective anti-JCV
treatment in the setting of PML.
● Therefore, treatment aims at reversing the immune deficiency to slow or stop the
disease progress. In patients on immunosuppression, this means stopping the drugs or
using plasma exchange to accelerate the removal of the biologic agent that put the
person at risk for PML.
● Treatment with highly active antiretroviral therapy (HAART) may prolong survival,
although in some instances this leads to PML-IRIS (Progressive multifocal
leukoencephalopathy immune reconstitution inflammatory syndrome). High-dose
glucocorticoid therapy is recommended for patients with PML-IRIS.
● Some reports also state some benefit with cytarabine or mirtazapine, the latter
especially in natalizumab-associated PML.
 Prognosis
● Prognosis is generally poor with an inexorable neurological decline leading to coma
and death occurring in the majority of patients with PML. If untreated, PML is usually
fatal within one year, often within 2 to 6 months.
● One-third to one-half of people with PML die in the first few months following diagnosis,
depending on the severity of their underlying disease. Survivors can be left with
variable degrees of neurological disability.
 CASE BASED
DISCUSSION
Arushi Sangwan (BMS16091743)
CASE:
A 21 year old woman was a known drug dealer and IV drug abuser. She was
brought to the emergency room after being found on the floor of her apartment by
her friends. Examination revealed an obtunded, febrile (39.6) woman; there were
two nail bed splinter hemorrhages, a grade II systolic ejection murmur, and a
palpable spleen tip.

The patient did not respond to commands and was in a sleep like state; her eyes
were tonically deviated to the left. She would open her eyes when pinched and
push away the examiner. Both optic discs were blurred and raised, there was a
right hemianopsia to threat and a right hemiparesis involving face, arm, leg.
PROVISIONAL DIAGNOSIS

● An intracerebral space occupying lesion due to infectious cause, secondary to

right sided bacterial valvular disease (Endocarditis)

● Reasoning:
SOL: She was found on the floor. Eyes were tonically deviated to the left.
Optic discs were blurred, there was right hemianopia and complete right sided
hemiparesis
VALVULAR DISEASE: Patient is a drug abuser. She was found with 2 nail
splinter hemorrhages, a grade II systolic ejection murmur, and a palpable
spleen tip.
DIFFERENTIAL DIAGNOSES- based on history
● Trauma (hemorrhage)- features like nail bed splinter hemorrhages, a grade II
systolic ejection murmur, and a palpable spleen tip do not support brain
hemorrhage

● Other infectious causes- tuberculosis/syphilis/cysticercosis

PROVISIONAL DIAGNOSIS→ Brain abscess
MORE DIFFERENTIAL DIAGNOSES - “MAGIC DR”
● Metastasis- patient presented with acute symptoms. No history of cancer/ no
symptoms of cancer/ no family history

● Abscess- Patient is a drug abuser, she has symptoms of a cerebral SOL as well
as signs of right sided endocarditis (most likely bacterial- Staph aureus)

● Glioblastoma Multiforme- patient presented with acute symptoms. GBM patient

will present with focal symptoms, not complete ipsilateral hemiparesis

● Infract (subacute)- no focal symptoms.

● Contusion- no history of trauma

(contd)
● Demyelinating disease- no signs and symptoms (spread in space and time,
recurrent, slowly progressing, focal signs, ataxia)

● Radiation Necrosis- no radiation history

INVESTIGATIONS
● FBC count with differentials and platelet count
● Erythrocyte sedimentation rate
● Serum C-reactive protein (CRP)
● Blood cultures & gram staining
● Lumbar tap- CSF culture and gram staining
● Abscess aspirate for gram staining, culture & therapeutic measures also
(via stereotactic CT or surgery)
● ECG, EEG to determine general health and other conditions
MANAGEMENT
● Empirical antibiotics (Cefotaxime/Ceftriaxone). If they are not available then
Penicillin or Chloramphenicol may be given.

● Added Vancomycin coverage if Staphylococcus aureus is suspected (like in

this patient). Done until susceptibility to Nafcillin is confirmed.

● Metronidazole can also be added if Bacteroides is suspected.

● Continuous monitoring with CT/MRI

● If antibiotics fail to resolve the abscess OR if abscess grows in size OR

abscess is >2 cm → antibiotics + CT guided surgical removal
(contd)
● Steroids can also be administered to decrease increased intracranial
pressure.

● COUNSELLING→ Patient needs to be counselled regarding her habits of

drug abuse. Continuous counselling or rehabilitation programs may be
offered. This is to prevent future recurrences & complications.

● FAMILY INTERVENTION→ family support can be crucial in this patient (due

to her young age of 21).

● Cognitive Behavioral Therapy→ to help patient understand thoughts, feelings

and associations behind the addictive behaviors
PROGNOSIS
● Good prognosis in this patient.

● Mortality has declined since the introduction of CT and MRI and the
development of newer surgical techniques.
Mortality rate is about 15%.

● The mortality is higher in immunocompromised, those who had a transplant,

and those with brain stem or deep hemispheric abscesses.

● Prognosis also depends on patient education to decrease the risk of relapse

and disease recurrence in the future.
REFERENCES
1. Davidson's Principles and Practice of Medicine 23rd edition
2. Brain Abscess Workup (https://reference.medscape.com/article/212946-
workup#c5)