This case presentation describes a 42-year-old man who presented with progressive weakness, spasticity, and pseudobulbar palsy in his upper and lower limbs over the past 6 months. Clinical examination revealed features of both upper and lower motor neuron involvement. Investigations including MRI, CSF analysis, and EMG were consistent with a diagnosis of motor neuron disease. The patient was found to be HIV positive. Given his clinical presentation and HIV status, he was diagnosed with HIV-associated generalized motor neuron disease. The pathogenesis of motor neuron disease in the context of HIV is not fully understood but may involve retroviral myelopathy or reactivation of endogenous retroviruses. Treatment involves continuation of HAART and supportive measures

1. Interesting Case Presentation
Dr. Ankit Raiyani
Medicine Dept.
LTMMC & GH

2. 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

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

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

5. 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

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+

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

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

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

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

11. 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

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

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

14. 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
1. 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

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 Tay-Sach’s ds, SOD1
mutation

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

17. References-
1. Moulignier A, Moulonguet A, Pialoux G, et al. Reversible ALS-like
disorder in HIV infection. Neurology 2001;57:995–1001
2. 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):697-703
5. 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.