Interesting Case Presentation

Dr. Ankit RaiyaniMedicine Dept.LTMMC & GH

History42 yr male married R/O Matunga illiterate tailorPresented with c/o• Difficulty in holding small objects in right hand with loss of

dexterity, progressive over 6 months and in left UL since last 2 mths

• Difficulty in walking due to tightness in both LL progressive over 6 mths

• Difficulty in speaking requiring more effort, more after talking for long time, progressively worsening over 6 mths

• Twitching in both UL since 4 mths, in LL since 2 mths• Difficulty in swallowing solids and liquids with nasal

regurgitation of liquids• increased frequency of micturition a/w urgency since 2 mths

No complaints of • Diplopia, blurring of vision• Headache, loss of consciousness,• Bowel, bladder incontinence• Loose motions, vomiting, abdominal pain• Tingling, numbness

Past history• k/c/o sero positive status, on ART (ZLN) since 2008,

CD4 count- 222 in march 2011• H/O trauma to right knee at the age of 16 year. Unable

to bend his right knee since then• Not a K/C/O diabetes, hypertension, • No P/H/O tuberculosisPersonal history- Ex alcoholic, ex tobacco chewer left since last 6 mthsFamily history- no h/o such illness in family

Examination

• Patient conscious oriented avg built, nourished

• P- 88/min reg, all pp well felt• BP- 118/74 mm of Hg, supine• No pallor, icterus, clubbing, LNpathy, edema• Poor oral hygiene, no oral candidiasis, no

linear bluish discoloration of gums• Skull, spine- NAD

CNS examination-• Conscious oriented co-operative• MMSE- 27/30, spastic dysarthria• Cranial nerves- – II to VIII – normal – IX, X- soft palate movement decreased , gag ++,

cough +– XI- SCM, trapezius b/l normal– XII- atrophy +, fasciculations+

• Motor system– Nutrition- wasting of the thenar and hypothenar muscles of

both hands– Patient sitting in bed with elbows flexed and wrist palmar flexed– fasciculations seen over both upper limbs, poly mini

myoclonus+– Tone - spasticity in BL LL > UL– Power-

• 3/5 in right UL, 4/5 in left UL, • Wasting of thenar and hypothenar muscles, dorsal interossei , abd

digiti minimi on both hands Rt > Lt

– Reflexes- • DTR- brisk in all 4 limbs• Sup-Abdominal, Cremasteric- absent, Plantar - both extensor

• No sensory deficits. Rhomberg’s –negative• No cerebellar signs• Gait- spastic, scissoringOther systems - NAD

• 35 year male with diffuse mixture of LMN and UMN weakness in both UL and LL with pseudobulbar palsy

• Clinical diagnosis- Motor Neuron Disease

Diff. diagnosis

• Motor neuron disease-– Paraneoplastic syndrome– Heavy metal poisoning– Paraproteinemia– Metabolic– HIV associated MND

• Pure motor polyradiculopathy

Investigations• Hb-12.1 gm%• WBC- 5100cells/cmm• DLC- P74/L24/M2• Platelets- 182000/cmm• MCV- 83 fl• FBS- 94 mg%• T. bili- 0.8 mg%• AST/ALT- 23/28 U/L• TP/Alb/Glob- 6.2/4.0/2.2 gm%• Bun/ Sr creat- 12/0.8 mg%• Na/K- 136/4.2 mmol/L• Ca/PO4- 7.4/3.6 mmol/L• Sr. TG/ Cholesterol- 104/ 158 mg%• Urinary BJP- negative• RBS- 93 mg%• T3/T4/TSH- 3.11/1.03/4.02 pg/dl• CD4- 222cells/µL• Stool R/M - NAD

• X-ray chest- NAD• CSF-WNL

– Routine/microscopy- no cells – Prot- 28mg% Sugar- 81.8mg%– Gm stain – no PC, no org, no growth– Cryptococcus- not seen, no growth– Culture – no growth

• EMG/NCV- s/o generalized anterior horn cell disease– Spontaneous Fibrillation, as well as polymorphic fasciculation in all groups

of muscles – Sensory nerve conduction findings normal– No e/o an underlying generalized peripheral neuropathy

• MRI Brain with screening of Cx spine- no significant abnormality

• Diagnosis- HIV associated generalised Motor Neuron Disease

• Treatment- – Continue HAART– T. Riluzole (50mg) BD– T. Baclofen (10mg) TDS– IV Vit B12/ Folate supplements– Physiotherapy/ occupational therapy

HIV associated Motor neuron disease

• HIV infection has been associated with increased incidence of ALS and other MND(1,2,3)

• Possible mechanisms- not completely understood1. Retroviral myelopathy(4)

2. Through HERV- K reactivation(5,6)-• HIV infection induces reactivation and replication of dormant Human

Endogenous Retro Virus-K10. (5)

• HERV-K has recently been implicated for pathogenesis of ALS though exact mechanism is not established.HERV-K pol transcripts were shown to be significantly increased in brain biopsy of patients with ALS compared to those with chronic systemic illness. (6)

• Whole spectrum of MND ( UMN/LMN/Both) can be seen in different cases

• Commonly involves patients not yet started on HAART

Diagnosis of exclusionAll other secondary causes of MND are to be ruled out• Structural- Cx myelopathy• Infections-tetanus, Lyme ds., poliomyelitis• Toxins/drugs- lead, aluminum, phenytion, strychnin• Immunologic- plasma cell dyscrasias, autoimmune

polyrediculoneuropathy• Paraneoplastic • Metabolic- hyperthyroidism, hyperparathyroidism, B12/Folate

def.• Errors of metabolism- adult onset Tay-Sach’s ds, SOD1 mutation

TreatmentNo specific treatment available• HAART- if patient not on ART. Starting HAART

has shown neurological improvement with decreasing viral load with antiretroviral therapy. (1,2)

• Supportive measures• Riluzole – may prolong life

References-1. Moulignier A, Moulonguet A, Pialoux G, et al. Reversible ALS-like disorder in

HIV infection. Neurology 2001;57:995–10012. Reversal of HIV-associated motor neuron syndrome after highly active

antiretroviral therapy. J Neurol 2001;248:233–4.3. Jubelt B, Berger JR. Does viral disease underlie ALS? Lessons from the AIDS

pandemic. Neurology 2001;57:945–6.4. Modi G, Ranchhod J, Hari K, Mochan A, Modi M. Non-traumatic myelopathy

-the influence of HIV. QJM 2011 Aug;104(8):697-7035. Garrison KE et al. T cell responses to human endogenous retroviruses in

HIV-1 infection. PLoS Pathog. 2007 Nov;3(11):e165.6. Douville R, Liu J, Rothstein J, Nath A. Identification of active loci of a human

endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann Neurol. 2011 Jan;69(1):141-51. doi: 10.1002/ana.22149.