Motor Neuron Disease
Kefah Al-Hayek, MD J.U.S.T.
Definitions
Motor neuron diseases:
Progressive degeneration and loss of motor neurons in the spinal cord with or without similar lesions in the motor nuclei of the brainstem or the motor cortex
Motor neuron disease = Amyotrophic lateral sclerosis Spinal muscular atrophy:
Only lower motor neuron signs
Amyotrophic lateral sclerosis (ALS)
A= without Myo= Muscle Trophic= Nourishment Lateral= side of the spinal cord Sclerosis= Hardening or scaring
ALS
Also known as Lou Gehrigs disease Degeneration of UMN and LMN Accuracy of clinical diagnosis ~ 95%
Epidemiology
Worldwide roughly the same prevalence 50 X lO-6 No identified consistent risk factors related to occupation, trauma, diet, or socioeconomic status Generally begins in 30-60s 5% of cases are familial in an autosomal dominant pattern
20% of familial cases map to ch. 21; mutations in the gene for superoxide dismutase (SOD)
Dementia and parkinsonism seem to increase in firstdegree relatives of patients with ALS
Pathogenesis
Sporadic ALS unknown Environmental factors have been suspected (Guam) Glutamate toxicity
Clinical Manifestations
Weakness : legs, hands, proximal arms, oropharynx Fasciculation Often hands are affected first, usually asymmetrically
Clinical Manifestations
Clinical Manifestations
Footdrop Muscle cramps (hypersensitivity of denervated muscle) Weight loss Respiration is usually affected late
Clinical Manifestations
Clinical Manifestations
Sensation is not clinically affected Bladder function is spared Combination of overactive reflexes with Hoffmann signs in arms with weak, wasted, and fasciculating muscles is virtually pathognomonic of ALS
Clinical Manifestations
Course is relentless and progressive without remissions, relapses, or even stable plateaus Death from respiratory failure, aspiration pneumonitis, or pulmonary embolism Mean duration of symptoms is about 4 years (27-43 months) ; 20% live > 5 years
Clinical Classification: I- Sporadic
Primary Lateral Sclerosis
Purely UMN Bilateral involvement of corticobulbar pathways Pseudobulbar affect Prominent dysarthria and dysphagia (LMN) LMN in limbs; anterior horn cell degeneration
Pseudobulbar Palsy
Progressive bulbar palsy
Progressive Spinal Muscular atrophy
Clinical Classification
II- Familial
AD AR X-linked
III- ALS-Parkinsonism-dementia complex
Laboratory Data
EMG evidence of active denervation in at least three limbs Nerve conduction velocities should be normal or nearly so Conduction block is rare in patients with frank upper motor neuron signs
Laboratory Data
MRI brain and spine CBC, KFT, LFT, TFT, serum electrophoresis Anti-GM1 antibodies
Diagnosis
Body divided into regions: Bulbar, cervical, thoracic and lumbosacral UMN & LMN signs in three regions
DDx
Multifocal motor neuropathy with conduction block
Conduction block in more than one nerve and not at sites of entrapment neuropathy Primarily affects the hands Asymmetric Men much more often than women Predominantly lower motor neuron Progresses more slowly than ALS Immunosuppressive drug therapy IVIG
DDx
Myasthenia gravis (MG)
Dysarthria and dysphagia Same age group as ALS Ptosis, ophthalmoparesis, diurnal fluctuation and remissions
DDx
Cervical spondylosis
Neck pain Sensory symptoms or signs in the hands No fasciculations in legs or tongue
DDx
MS B12 def HIV Pseudobulbar Palsy (MS and bilateral strokes) Benign fasciculation and cramps
Medical students, physicians, and other medical workers No weakness nor wasting ALS almost never start with this syndrome
Rx
No effective drug therapy Riluzole (Rilutek)
Glutamate inhibitor Prolongs life by 3 to 6 months No visible effect on function or quality of life
Symptomatic (sialorrhea, dysphagia, tracheostomy) Emotional support Immunosuppressive therapy
Only for lymphoproliferatlve disease, monoclonal gammopathy, conduction block or high titers of antibodies to GM, or MAG
Famous people with ALS
Steven Hawking: Smartest man alive Proved Einstein's Theory of Relativity He currently uses an electric wheelchair to get around A computerized voice synthesizer operated by facial muscles in order to speak
