clinical

1. CURRENT CONCEPTS ABOUT
MOTR NEURON DISEASE
DR. PIYUSH OJHA
DM RESIDENT
DEPARTMENT OF NEUROLOGY
GOVT MEDICAL COLLEGE, KOTA

2. • Loss of Dexterity
• Loss of muscle strength (mild weakness)
• Spasticity
• Pathological Hyperreflexia
• Pathological Reflexes (Babinski, Hoffman sign, loss of
Abdominal reflexes)
• Increased reflexes in an atrophied limb(Probable UMN
sign)
• Pseudobulbar palsy (emotional lability, brisk jaw jerk,
hypeactive gag, forced yawning, snout reflex, suck
reflex, slow tongue movements, spastic dysarthria)
SIGNS & SYMPTOMS OF UMN
INVOLVEMENT

3. SIGNS & SYMPTOMS OF LMN
INVOLVEMENT
• Loss of muscle strength (moderate to severe
weakness)
• Muscle atrophy
• Hyporeflexia
• Muscle hypotonicity or flaccidity
• Fasciculations
• Muscle cramps

4. AMYOTROPHIC LATERAL SCLEROSIS
• Also k/a Charcot Disease/ Motor Neuron Disease/ Lou
Gehrig Disease.
• First described by Jean Martin Charcot in 1869.
• Neurodegenerative disorder of undetermined etiology.
• Primarily affects the motor neuron cell populations in
the motor cortex, brainstem and spinal cord.
• Progressive disease with most patients eventually
succumb to respiratory failure.
• 5-10% cases are familial- most common inheritance
AD.

5. • In sporadic spinal ALS, M:F ratio is 1.2-1.4:1.
• Slight female preponderance in Bulbar onset
variety.
• The mean age of onset is 43–52 years in familial
and 58–63 years in sporadic cases of ALS.
• Mean disease duration from symptom onset to
death is approx 3 years.
• Roughly 1 in 5 patients survive to 5 years and 1 in
10 patients survive to 10 years.
• Smoking appears to be an independent risk factor
for sporadic ALS (Armano,2009).

6. PATHOPHYSIOLOGICAL PROCESSES IN ALS
• Excitotoxicity - Excessive postsynaptic glutamate induced
stimulation of glutamate receptors such as NMDA & AMPA →
massive calcium influx → nitric acid formation and neuronal
death .
• Oxidative stress - Fibroblast culture from MND patients shows
increased sensitivity to oxidative damage - accumulation of
free oxygen species → cell death.
• Mitochondrial defect - Abnormalities of mitochondrial
morphology and biochemistry reported in sporadic MND
patients, in SOD1 transgenic mice, and in cellular models .
• Impaired axonal transport - reported in transgenic mice.

7. • Abnormal Neurofilament aggregation
• Protein aggregation - Intracellular inclusions have been
observed in MND. The evidence is still unclear if these
proteins are toxic or beneficial to the cell.
• Inflammatory dysfunction - Evidence suggests the
possibility of an inflammatory process.
• Deficits in neurotrophic factors and dysfunction of
signaling pathway
• Deficits in levels of neurotrophic factors, e.g., IGF-1,
have been reported in MND.
• Apoptosis - The final process in MND leading to
neuronal death is said to closely resemble apoptosis,
and markers of apoptosis have been detected in the
later stages of the disease and animal models.

8. PRACTICAL CLASSIFICATION OF
AMYOTROPHIC LATERAL SCLEROSIS
• Sporadic or Acquired ALS
• Classic (spinal onset) ALS
• Mills Hemiplegic variant
• Pseudoneuritic presentation
• Flail-arm presentation
• UMN onset
• LMN onset
• Bulbar onset
• Dyspnea onset
• Progressive muscular atrophy
• Progressive bulbar palsy
• Western pacific ALS

9. • Familial ALS :
• ALS1 : SOD1 missense mutation :Chr 21, adult, AD
• ALS2 : ALSIN mutation,Chr 2q, juvenile onset
• ALS4 : Sentaxin gene , Chr 9q , juvenile onset, AD
• ALS3,5,6,7,8,9,10,11, X linked AD ALS
• FTD-ALS overlap
• ALS-FTD 1,2,3
PRACTICAL CLASSIFICATION OF
AMYOTROPHIC LATERAL SCLEROSIS

10. • Pathological hallmark of ALS – degeneration
and loss of motor neurons, with astrocytic
gliosis and microglial proliferationin the
presence of intraneuronal inclusions (Bunina
bodies) in degenrating neurons and glial cells.

11. CLINICAL FEATURES OF ALS
• Typical clinical presentation- Patient with
progressive motor deterioration manifesting with
both UMN and LMN symtoms and signs.
• i.e. combination of marked weakness and wasting
but with brisk reflexes, spasticity and pathological
reflexes.
• Muscle weakness begins in a focal area before
involving contiguous muscles in same region and
then another region. So may resemble Focal
mononeuropathy (Pseudoneuritic or Flail-leg
presentation)

12. • More commonly, weakness occurs in a limb muscles
supplied by multiple nerves (Monomelic presentation)
• Onset of muscle weakness is more common in upper
extremity than lower extremity (Classic , Spinal ALS).
• Bulbar onset ALS -25% cases
• Weakness starting in respiratory muscles – 1-2% cases
• Sometimes weakness restricted to one side (Mills
Hemiplegic variant)
• 10 % patients present with bilateral upper extremity
wasting (Flail Arm/ Flail person in the Barrel variant)
• Reflexes may be retained or even brisk in markedly
atrophied muscles.

13. • Fasciculations – not commonly the presenting feature
– but develops in all patients soon after onset –
absence should prompt to consider an alternative
diagnosis.
• Muscle cramps – a very common symptom.
• In case of dysphagia, Weight loss is often rapidly
progressive – represents poor intake along with ALS
cachexia.
• Sleep disturbances from hypopnea and apnea are
common.
• Cognitive dysfunction occurs in 20–50% of cases, and
5–15% develop dementia usually of Frontotemporal
type.

14. • Atypical features :-
– Extrapyramidal dysfunction
– Eye movement abnormalities
– Autonomic disturbances
– Abnormal sphincter control are extremely rare in
ALS and their presence should always prompt to
consider alternative diagnosis.

15. • Poor prognostic factors in ALS-
– Older age at onset
– Bulbar onset pattern
– Shorter interval between onset and clinical diagnosis
(aggressive presentation)
– Rapid progression rate as assessed on return visits
– Low BMI
– FTD-ALS presentation
– Dyspnea at onset
– Rapid rate of decline in pulmonary function.

16. LABORATORY STUDIES
• Diagnosis mainly on history and physical
examination alone
• Owing to seriousness of the diagnosis,
ancillary tests to rule out other possibilities.
• CBC, Serum CPK, Ca, Phosphate, Mg, VDRL,
HIV, GM1 autoantibody titres, ESR, serum
protein electrophoresis, ACE levels, HbA1c,
thyroid function test, vit B12 levels.

17. • Electrodiagnostic examination –
– Invaluable tool in investigation of ALS.
– Serves as an adjunct to clinical examination.
– Determines the presence and extent of LMN involvement.
– No findings are ALS specific, can strongly support
diagnosis.
– Sensory NCS is generally WNL.
– Motor NCS may be normal, although conduction velocities
and CMAP amplitude may diminish with extent of motor
axonal loss.
– No evidence of conduction slowing or block.
– Severe motor axonal loss may give “Generalised Low
motor – normal sensory “EDX pattern –suggesting poorer
prognosis.

18. • EMG examination –
– Combination of Acute (positive sharp waves and
fibrillation potentials) and Chronic ( reduced
neurogenic firing pattern with evidence of increased
amplitude and duration, polyphasic motor unit
potentials).
– Changes are widespread, not limited to any single root
or peripheral nerve distribution.
– Fasciculation potentials are common.
– Recent Awaji-Shima algorithm for neurophysiological
diagnosis of suspected ALS stresses the importance of
Fasciculation potentials as an evidence of acute
denervation.

19. • SPLIT HAND PHENOMENON –
– In some patients , EDX reveals severe changes in
muscles of lateral hand (Thenar eminence) but
relative sparing of medial hand (Hypothenar
eminence).
• EDX studies should be carried out in 3 of the 4
regions of Neuraxis (bulbar, cervical, thoracic and
lumbodacral)
• Neuroimaging to rule out other causes.
• Erect forced vital capacity – most commonly
measure index of pulmonary function in ALS
• Supine FVC – more accurate assessment of
diaphragmatic weakness.

20. • Maximal inspiratory pressure and nocturnal
oximetry – more effective for estimation of
nocturnal hypoventilation.
• Trans-diaphragmatic sniff pressure(sniff Pdi)
and Sniff nasal pressure (SNP) – useful
indicators of hypercapnia and nocturnal
hypoxemia.

21. DIAGNOSTIC CRITERIA FOR CLINICAL
DIAGNOSIS OF ALS
• DEFINITE ALS –UMN and LMN signs in at least 3 regions
(bulbar and 2 spinal regions or 3 spinal regions without
bulbar)
• PROBABLE ALS - UMN and LMN signs in 2 regions, with
some UMN signs rostral to LMN signs
• PROBABLE ALS, Lab supported - UMN and LMN signs in
1 regions, with UMN signs alone in another region and
EMG evidence of involvement in at least 2 limbs.
• POSSIBLE ALS - UMN and LMN signs in 1 region, or
UMN signs alone in 2 or more regions; or LMN signs
are rostral to UMN signs.

22. • FAMILIAL ALS , Lab supported – otherwise
unexplained UMN or LMN signs an at least
region, with SOD1 gene mutation in the
proband or a positive family history of family
member with a disease causing SOD1 gene
mutation.

23. • Multidisciplinary team approach
• Both AAN and EFNS recommend MDC care setting
for patients with MND, with the current EFNS
guidelines recognizing the benefit of MDC approach
in improving survival, reducing medical
complications, and improving the quality of life of
patients and their caregivers.
TREATMENT OF ALS

24. • Multidisciplinary clinic team:
– Neurologist
– Respiratory physician
– Gastroenterologist
– Rehabilitation medicine physician
– Social counselor
– Occupational therapist
– Speech therapist
– Respiratory therapist
– Specialized nurse
– Physical therapist
– Dietitian
– Psychologist
– Dentist and
– Palliative care physician

25. TREATMENT OF ALS
• RILUZOLE – only FDA approved drug (1996)
• Principally act as antiglutamate agent by blocking its
presynaptic release.
• Slows the disease progression but doesnt stop the underlying
disorder.
• Studies showed significantly longer survival benefit with
Riluzole 50 mg compared to placebo. (disproportionately
beneficial in Bulbar onset disease and elderly)
• 100 mg Riluzole resulted in 9% increase in probability of
survival for 1 year and prolongs median survival by 2-3
months when taken for 18 months.
• Side effects :- fatigue, GI upset, dizziness, deranged LFTs
• To minimize side effects, recommended to start with
50mg/day in evening and increased to twice a day dose after
1-2 weeks.

26. • Recombinant human insulin-like growth factor-1 (rhIGF-1)
has been proposed as a Modifying Drug Therapy in MND
following its ability to promote spinal motor neuron survival
after excitatory amino acid induced death in animal models.
• A Cochrane review of the benefit of rhIGF-1 on disease
progression using 3 studies involving 799 MND patients
observed low quality evidence of improved QOL scores at 9
months, with no impact on survival.

27. PHYSICAL REHABILITATION
• Goal of Physical Rehabilitation- to improve patient’s
ability to carry out ADL for as long as possible without
causing undue physical or emotional strain.
• also prevents complications secondary to disuse and
immobilization eg. Frozen shoulder
• Occupational therapists – an important member of ALS
care team
• Various assistive and adaptive devices to improve
mobility and comfort and help carry out ADL like
walkers, wheelchairs, splints etc.
• Evaluation of home environment and customized home
epuipment.

28. SPEECH AND COMMUNICATION MANAGEMENT
• Speech and communication dysfunction- one of the
most serious factors reducing quality of life.
• Role of speech pathologists to assess speech and
communication soon after diagnosis is established.
• AIM – maintain independent communication a long as
possible.
• Energy conservation techniques
• Nonverbal techniques (gestures, body language)
• Assistive and augmentative devices (alphabet/picture
boards to voice synthesizers)

29. NUTRITIONAL CARE
• Dysphagia may occur in MND due to loss of coordination,
weakness of muscles of mastication, tongue, and impaired
swallowing.
• Complicated by weight loss, distressing choking, prolonged
effortful meal times, frequent aspiration, and increase risk of
chest infection.
• Malnutrition positively correlates with a shortened survival
rate and is a poor prognostic factor.
• So nutritional assessment to be done by an experienced
Dietician on every visit.
• Initially, patient adviced to change form and texture of food
and use a high calorie food supplement.
• In the later stages feeding can be through nasogastric tube
(NGT) or gastrostomy insertion.

30. • Guidelines of both the AAN and EFNS recommend the use of
gastrostomy in MND.
• Methods of gastrostomy insertion include
– Percutaneous endoscopic gastrostomy (PEG)
– Radiologically inserted gastrostomy (RIG), and
– Per-oral image-guided gastrostomy (PIG).
• PEG – most commonly used.

31. • PEG improves quality of life and prolongs survival.
• Helps in maintaining weight/BMI.
• Although a simple procedure but may complicate due to
impending respiratory failure.
• Guidelines advocate PEG tube placement in consenting
patients with dysphagia whose seated predicted FVC is > 50%,
but may also be performed in patients with FVC<50% if NIPPV
is also used during the procedure.
• Radiologically inserted gastrostomy and percutaneous
radiologic gastrostomy are alternative approaches.
• Purpose of enteral feeding is to provide calories and fluid.
• If recurrent aspiration of PEG contents -> percutaneous
enteral jejunostomy (PEJ) should be done

32. RESPIRATORY CARE
• Respiratory failure – most common cause of death in ALS.
• Denervation weakness of respiratory muscles results in
ineffective cough, retention of secretion, and
hypoventilation, and it is an important determinant of QOL.
• Onset of respiratory impairment is marked by sleep
disordered breathing (SDB) which results in early morning
headaches, nonrefreshing sleep, daytime somnolence,
dyspnea, orthopnea, poor concentration, and fatigue.
• Assisted ventilation can be provided using invasive
technique via tracheostomy or NIV using face or nasal
mask.

33. • Studies have shown that NIV prolongs median survival.
• A review by NICE has further confirmed the cost
effectiveness of NIV used for MND patients .
• NIV improves gas exchange, alleviates symptoms of
CO2 retention, and improved QOL.
• Evidence suggest that patient to be offered NIV at
onset of dyspnea when FVC falls to <50%.
• Claustrophobia, anxiety, excessive salivation, nasal
bridge soreness, and abdominal bloating are some of
the problems associated with NIV use in MND patients

34. • Invasive ventilation or tracheostomy ventilation (TV) can
also be used .
• It is used in patients with severe bulbar dysfunction who
cannot tolerate NIV or in patients previously using NIV whose
respiratory function has deteriorated to a point where NIV is
not tolerated.

35. • Respiration can also be assisted using an electrical
stimulation of the diaphragm to produce contractions
(diaphragmatic pacing).
• Procedure originally meant for patients with cervical
spine injury, but still experimental in MND.
• Effective only if the diaphragm retains some
innervation .
• The diaphragmatic pacing in patients with respiratory
muscle weakness due to ALS study (DIPALS) is an
ongoing RCT assessing the efficacy of diaphragmatic
pacing among MND patients in some UK hospitals.

36. • Respiratory weakness also impairs cough -> results in
recurrent chest infection, which is the leading cause of
hospitalization in MND.
• The strength of the patients’ cough is assessed with a
peak flow meter and reported as suboptimal if the
peak cough-flow (PCF) is less than 270/min.
• Cough can be augmented using intensive
physiotherapy and manoeuvres like tussive squeeze
and mechanical in-exsufflator (MI-E).
• Evidence for MI-E is weak, but it has been suggested
that it could be effective in MND patients for cough
management.

37. • Patients and family members should be
counseled that all forms of ALS will eventually
end by ventilatory failure.
• Patient should be made aware that although
ventilation via a tracheostomy may
indefinitely prolong life, there is no effect on
disease itself.

38. OTHER SYMPTOMATIC MANAGEMENT
• Sialorrhoea :-
– Excessive salivation is common in MND as bulbar
dysfunction worsens and can be embarrassing or result in
aspiration.
– Amitriptyline, Atropine, Botulin toxin type-B (BTX-B), and
external irradiation of the salivary gland have all been tried
in the control of sialorrhoea.
– A double-blind control trial BTX-B injected into the parotid
and mandibular gland of 20 patients with refractory
sialorrhoea achieved 82% reported improvement
compared to 38% among those who received placebo at
2 months (𝑃< 0.05).

39. – Costa et al. also evaluated the efficacy and safety of BTX-B
in the treatment of sialorrhoea in patients with a bulbar
onset MND in an open-labeled prospective study that
involved the injection of BTX-B into the parotid and
submandibular glands.
– They observed that most patients reported a better quality
of life while on treatment and a mean reduction of
symptom severity of 70%.
– The most commonly reported side effects include viscous
saliva, local pain, chewing weakness, and respiratory
infection.

40. • Pseudobulbar Effect:-
– Observed in up to 50% of MND patients .
– Yawning, weeping, and laughing are the characteristic
presentation.
– Pseudobulbar affect has a negative impact on QOL.
– Small placebo controlled trials and case series have
observed the effectiveness of SSRIs and TCAs in controlling
this symptom .

41. – Pioro et al. evaluated the treatment of pseudobulbar affect
in patients with MS and MND in a RCT using 30/10 mg and
20/10 mg Dextromethorphan plus ultra-low-dose
quinidine.
– They reported that dextromethorphan plus ultra-low-dose
quinidine is effective in reducing the frequency and
severity of symptoms and improving patients’ quality of
life especially at the dose of 30/10 mg combination
when compared with placebo.
– EFNS recommends Citalopram (SSRI) and Amitriptyline
(TCA) for treatment of troublesome cases of
pseudobulbar affect.
– A fixed dose combination of dextromethorphan
/quinidine (30 mg/30 mg) is the recommended
treatment option of AAN.

42. CRAMPS :-
• Usually troublesome particularly at night.
• A RCT failed to support the efficacy of
tetracannabinoid in treating moderate to severe
cramp.
• A small open-labeled pilot study confirmed that
levetiracetam is useful for treatment of cramps in
MND patients.
• Modalities such as massage, physical exercise,
hydrotherapy, heated pools, and drugs like
carbamazepine, diazepam, phenytoin, and verapamil
have all been tried without any conclusive evidence.
• EFNS recommends levetiracetam, quinine sulfate, and
physical therapies for management of cramp in MND.

43. SPASTICITY :-
• Physical therapy is the main treatment modality
for spasticity that has its usefulness established
from RCTs.
• Physical therapy methods in use include
therapeutic exercise, stretching, positioning,
casting, and biofeedback.
• Other interventions with no controlled trial
evidence include heat/cold therapy,
hydrotherapy, ultrasound, electrical stimulation,
and rarely surgery can be used.
• Intrathecal Baclofen is the drug of choice in
intractable cases.

44. • Drugs such as Dantrolene, Tetrazepam, and Tizanidine
have not been tested in MND in clinical practice but are
recommended by EFNS.
• Nonpharmacological treatment modalities should first
be deployed before pharmacological interventions are
introduced if symptoms do not improve.
• These drugs should be used with caution in MND
patients as they can cause depression of respiration
and worsening of weakness.
• Physical therapy can be combined with one or more of
the antispasticity drugs.

45. Insomnia and Fatigue :-
• Common in the final stages of MND probably due to
cramps, pain, and respiratory impairment .
• Amitriptyline and Zolpidem are some of the
medications used in practice without being tested.
• Fatigue is potentially debilitating symptom.
• An open-labeled trial confirmed the effectiveness of
Modafinil in the treatment of fatigue in MND

46. REFERENCES
• Bradley’s Neurology in clinical practice 6th edition
• Adams & Victor’s Principles of Neurology 10th edition
• Multidisciplinary Interventions in Motor Neuron Disease :
Journal of Neurodegenerative diseases ,2014
• EFNS guidelines on the Clinical Management of Amyotrophic
Lateral Sclerosis (MALS)– revised report of an EFNS task force :
European Journal of Neurology 2012
• Motor neuron disease: systematic reviews of treatment for
ALS and SMA : British Medical Bulletin 2010
• Practice Parameter update: The care of the patient with
amyotrophic lateral sclerosis: Drug, nutritional, and
respiratory therapies (an evidence-based review) :AAN, 2009

49. • MND term coined by Brain in 1969.

50. PRIMARY LATERAL SCLEROSIS
• First described by Erb in 1875.
• Rare UMN disease variant
• 2-4% of all cases of ALS
• Traditionally distinguished by lack of LMN involvement.
• Pringle Criteria(1992) – disease be restricted to UMN
system for at least 3 years from the time of clinical onset.
• Current status – 4 years duration during which there is
neither clinical or electrophysiological evidence of LMN
involvement.
• LMN involvement may occur later and may require
reclassification - thus need for constant longitudinal review
of each case.

51. • Typically presents in 5th decade (about a decade
younger than typical MND/ALS patients)
• Very slowly progressive spastic paraparesis
spreading to upper limbs and eventually causing
Pseudobulbar Palsy.
• Rarely onset may be in Bulbar system or follows a
slowly ascending or descending Hemiplegic
pattern (Mills Hemiplegic Variant).
• Bladder dysfunction usually late (rare)

52. • Although muscle weakness is present, main
defects are due to spasticity in Dexterity and
Gait.
• Muscle atrophy – rare and late feature.
• No clinically detectable sensory changes.
• Subtle cognitive changes may occur due to
Frontal cortical involvement but Dementia is
not a prominent feature.
• Respiration is usually unimpaired.

53. • Prognosis –significantly better than MND/ALS
• One series – median disease duartion of 19 years.
• Underlying pathogenesis remains undefined.
• A diagnosis of Exclusion.
• D/Ds :- cervical spondylotic myelopathy, MS, HIV
melopathy, HTLV -1 myelopathy, Lyme disease, Syphilis,
Adrenomyeloneuropathy, Paraneoplastic (Ca Breast),
Sjogren syndrome
• Treatment – No specific pharmacotherapy available.
• Supportive treatment – Antispasticity drug – Baclofen,
Tizanidine
• Pseudobulbar affect- SSRIs, TCAs

54. HEREDITARY SPASTIC PARAPLEGIA
• Also k/a Familial Spastic Paraplegia
• Genetically and clinically heterogenous group of
disorder
• Common feature – progressive worsening spasticity of
lower limbs, often with variable degree of weakness.
• Characteristic pathology – retrograde degeneration of
the longest nerve fibers in corticospinal tracts and
posterior columns.
• Most common mode of inheritance – AD
• May also have AR or X linked inheritance.

55. • Most cases present in 2nd to 4th decade.
• Clinical syndrome – Pure from & Complicated form
• Pure form – only lower limb spasticity.
• Some pure forms may become complicated later on.
• Complicated forms – optic neuropathy, pigmentary
retinopathy, deafness, ataxia, amyotrophy, Icthyosis,
peripheral neuropathy, dementia, autoimmnune
hemolytic anemia/ thrombocytopenia, extrapyramidal
dysfunction, mental retardation and bladder
dysfunction

56. • Most pure HSP – autosomal dominant
• Complicated forms – autosomal recessive
• 40-45% families – SPAST gene mutation on chr
2p22-21
• SPG3A gene mutation- Autosomal dominant,
early onset (<10 years) pure HSP
• Spastic Paraplegia 17 (Silver Syndrome) –
mutation in Seipin gene on Chr 11q12-q14 – Aut
Dominant complicated form of HSP with distal
foot and hand amyotrophy, beginning in late
teens to early 30s.

57. • Diagnosis of HSP – positive Family history in the setting
of progressive gait disturbance, evidence of lower limb
spasticity and sparing of craniobulbar functions.
• In the absence of family history or a demonstration of
a known mutation – D/Ds include Structural causes
(cerebral palsy, hydrocephalus, myelopathy),
degenerative/infiltrative/inflammatory diseases
(MS,ALS,SCA, leukodystrophy),
infections(Syphilis,HIV,HTLV), levodopa responsive
dystonia, SACD, vitamin E deficiency, Cu deficiency,
Lathyrism and Paraneoplastic disorder.

58. TROPICAL SPASTIC PARAPARESIS / HTLV-1
ASSOCIATED MELOPATHY(HAM)
• Chronic insidiously progressive myelopathy that typically
begins after 30 yrs (may occur in 1st decade also) .
• Occurs in 2.5-3.8% of infected patients with HTLV-1 virus.
• Patient complains of slowly progressive spastic paraparesis
along with lower extremity paresthesias, painful sensory
neuropathy, bladder dysfunction and occassionally optic
neuropathy.
• LMN signs and objective sensory findings are absent.
• MRI – may reveal increased signals on T2 weighted sequences
in periventricular white matter and atrophy of thoracic cord.
(not specific for HTLV-1).
• Definitive diagnosis – HTLV-1+ serology in blood and CSF.
• At present, no antiviral agents effective against HAM.
• A case report suggest partial benefit with plasmapheresis.

59. ADRENOMYELONEUROPATHY
• X linked recessive disorder.
• Mutation in ABCD1 gene on chromosome
Xq28 – harmful accumulation of Very long
chain fatty acids in affected cells – interfere
with membrane components of both neurons
and axons.

60. • ADRENOLEUKODYSTROPHY –
– most common phenotype
– inflammatory disorder of brain and spinal cord
– Affects young boys 4-8 yrs age.
– Severe adrenal insufficiency, progressive cognitive
deterioration, seizures, blindness, deafness and
spastic paraparesis.

61. • ADRENOMYELONEUROPATHY –
– Noninflammatory axonopathy of spinal cord
– Involve descending corticospinal tracts in thoracic and
lumbosacral regions and ascending posterior columns
in cervical region
– Slowly progressive spastic paraparesis and mild
polyneuropathy in adult men (late 20s) with or
without sensory symptoms and sphincter
disturbances.
– adrenal insufficiency may be present and may
precede neurological symptoms by several years.

62. • Adult female carriers – slowly progressive spastic paraparesis.
• Should be suspected in males with progressive sensorimotor
deficits in legs and a family history of myelopathy .
• History of memory loss or attention deficit disorder or
idiopathic childhood epilepsy or primary adrenal failure also
gives a clue.
• Sural nerve biopsy – loss of both myelinated and
unmyelinated axons with some degree of onion bulb
formation.
• Ultrastructural examination – characteristic inclusions (empty
lipid clefts) in schwann cell cytoplasm.
• NCV – predominantly axon loss type sensorimotor
polyneuropathy.
• Diagnostic test of choice – demonstration of increased levels
of VLCFAs levels in plasma, RBCs or cultured skin fibroblasts.
• No specific therapy for adult onset adrenomyeloneuropathy.

63. POSTPOLIO SYNDROME/ PROGRESSIVE
POSTPOLIOMYELITIS MUSCULAR ATROPHY
• Reported incidence of 28.5-64% among polio survivors.
• By definition, patient must have recovered from acute
poliomyelitis , and disease course been stable for at
least 10 years after the recovery.
• When this is satisfied, PPMA is a diagnosis of exclusion.
• Complains of progressive symptoms of new muscle
weakness and new atrophy in previously affected
muscles or sometimes in muscles apparentaly not
affected by original poliomyelitis.
• Generalized fatigue is characteristic and most disabling
(also k/a Polio Wall)

64. • Other symptoms – pain, sleep disturbances, cold
intolerance, depression, hypoventilation, dysphagia and
dysarthria.
• New symptoms should have persisted for at least one year
to consider the diagnosis.
• Examination – focal and asymmetrical muscle weakness
and atrophy, Fasciculations
• EMG – reduced number of motor units and chronic
neurogenic motor unit potentials.
• Giant motor unit potentials may be seen indicating chronic
denervation and reinnervation.
• NCV – low maximum CMAPs
• Sensory NCS is normal.

65. • Muscle biopsy – acute and chronic neurogenic
atrophy with marked group fiber atrophy and
fiber type grouping
• Treatment is symptomatic and supportive.