Motor Neuron Disease in HIV Positive patient

Interesting Case Presentation: 

Interesting Case Presentation Monday Unit Dr. Ankit Raiyani

History: 

History 42 yr male married R/O Matunga illiterate tailor Presented 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

Slide 3: 

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

Slide 4: 

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 tuberculosis Personal history- Ex alcoholic, ex tobacco chewer left since last 6 mths Family history- no h/o such illness in family

Examination: 

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

Slide 6: 

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+

Slide 7: 

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

Slide 8: 

No sensory deficits. R homberg’s –negative No cerebellar signs Gait- spastic, scissoring Other systems - NAD

Slide 9: 

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: 

Diff. diagnosis Motor neuron disease- Paraneoplastic syndrome Heavy metal poisoning Paraproteinemia Metabolic HIV associated MND Pure motor polyradiculopathy

Investigations: 

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

Slide 12: 

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

Slide 13: 

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 associated Motor neuron disease HIV infection has been associated with increased incidence of ALS and other MND (1,2,3) Possible mechanisms- not completely understood Retroviral myelopathy (4) 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

Slide 15: 

Diagnosis of exclusion All 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 T ay-Sach’s ds, SOD1 mutation

Slide 16: 

Treatment No 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

Slide 17: 

References - Moulignier A, Moulonguet A, Pialoux G, et al . Reversible ALS-like disorder in HIV infection . Neurology 2001;57:995–1001 Reversal of HIV-associated motor neuron syndrome after highly active antiretroviral therapy . J Neurol 2001;248:233–4. Jubelt B, Berger JR. Does viral disease underlie ALS? Lessons from the AIDS pandemic . Neurology 2001;57:945–6. Modi G, Ranchhod J, Hari K, Mochan A, Modi M. Non-traumatic myelopathy - the influence of HIV . QJM 2011 Aug;104(8):697-703 Garrison KE et al. T cell responses to human endogenous retroviruses in HIV-1 infection . PLoS Pathog. 2007 Nov;3(11):e165 . 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 .