Amyotrophic Lateral Sclerosis Semmelweis Univ.pdf

Institute of Genomic Medicine and Rare Disorders
Semmelweis University

Head of department: Prof. Dr. Mária Judit Molnár
25-29. Tömő str., Budapest, Hungary, H-1083


Tel:+36-1-459-
1483

Email: [email protected]  mmelweis-univ.hu

Amyotrophic Lateral Sclerosis Protocol

Amyotrophic  Lateral  Sclerosis  (ALS,  G1220)  is  a  rapidly  progressive,  invariably  fatal
neurodegenerative disorder. It belongs to the motor neuron diseases where the motor neurons (α
motor neurons) degenerate gradually and loss their function. Incidence is around 1-3/100.000/year
and prevalence is  cc. 4-10/100.000/year. Average time of survival: 2-4  years. Hereditary ALS in
10 percent and SOD1 mutation can be detected in 1-2% of cases.
The appearance of ALS is characterized by muscle weakness, cramps, fasciculation and the loss of
ability of voluntary muscle movements. Symptoms begin focally, they become generalized finally.
Peripheral  and  central  signs  are  simultaneously  present.  Sensory  functions,  cognitive  ability,  eye
movements and vegetative functions are spared (Hirano criteria).
Diagnostic evaluation (Supplement 2)
Anamnesis:
-  Age (usually 55ys<)
-  Gender (late onset: female:male 2.5:1; early onset: 1.4:1)
-  Familial history
-  Various expositions (drugs, chemicals, toxins)
-  Laboratory investigation (to rule out other causes of motor neuropathy)
Routine neurological examination
Negative findings
-  sensory impairment is absent
-  eye movements are intact
-  normal vegetative function
-  normal cognitive ability
Positive findings
-  atrophy and paresis of muscles
-  PNS: fasciculation, fibrillation in tounge, dysarthria, dysphagia
-  CNS: bris reflexes, pyramidal signs, spasticity
Electrophysiological examination
Sensory functions
-  ENG and SEP are normal
Motor functions
-  ENG:
o  asymmetric CMAP differences (axonal)
o  increased F wave latency
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Institute of Genomic Medicine and Rare Disorders
Semmelweis University

Head of department: Prof. Dr. Mária Judit Molnár
25-29. Tömő str., Budapest, Hungary, H-1083


Tel:+36-1-459-
1483

Email: [email protected]  mmelweis-univ.hu

EMG:
Most important diagnostic tool in determining diagnostic certainty of ALS
Decreased motor unit recruitment with rapid firing of a reduced number of motor units,
and/or  large  amplitude,  long  duration  MUP  with  or  without  evidence  of  remodeling
(increased  number  of  phases)  in  combination  with  abnormal  spontaneous  activity
including  positive  sharp  waves  (PSWs),  fibrillations,  and/or  fasciculation  potentials
(FP).The  most  recent  consensus  update  of  the  El  Escorial  Criteria  (discussed  below)
assigned equivalent clinical significance to FP, PSWs, and fibrillation potentials.
Briefly:
o  signs of denervation (fibrillation, positive sharp waves)
o  signs  of  degradation  of  motor  neurons  (fasciculation)  –  DDx  benign
fasciculation
o  abnormal single fiber / repetitive stimulation
o  Motor unit number estimation – the number of motor units and thus the number
of lower motor neurons innervating a muscle; can be followed up
o  (El Escorial and Awaji-shima criteria)
-  MEP
o  Signs of upper motor neuron degradation

Neuroimaging
-  MR – craniospinal
o  hyperintens signal on MR – focal signal in corticospinal tract, cerebral peduncle
and internal capsule (present in not all ALS patient)
o  spinal cord – gliosis

Other

-  Lumbpal punction

Management:
There  is  no  curative  options  in  ALS.  Progression  can  be  slowed  down  and  life  quality  can  be
improved.
Medical treatment:
-  riluzol – anti-glutamate drug and improve the survival in ALS. Modest effect is always
present - smallest effect is up to 170 day compared to controls. Dosage: 100 mg/die

-  antisense nucleotide treatment – in research

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Institute of Genomic Medicine and Rare Disorders
Semmelweis University

Head of department: Prof. Dr. Mária Judit Molnár
25-29. Tömő str., Budapest, Hungary, H-1083


Tel:+36-1-459-
1483

Email: [email protected]  mmelweis-univ.hu

Supportive treatments (Figure 1.):
-  Nutrition
o  PEG (! calorie intake should increase cautiously !)
o  Prognostic factors:
  High calorie diet is better - increase survival time vs. low calorie diet
  Weight loose of more than 5 kg in 3 month worsen the survival rate
  Higher LDL/HDL ratio, increased triglyceride increase the survival
-  Respiration
o
o  Non-invasive ventilation - slightly better bulbar function
o  Regardless the type of mask which is used, survival rates are the same (! mask
must be used properly !)
o  Diaphragm pacing system is unprofitable for the patient
-  Cramps
o  Mexiletine  –  300  mg/die  is  the  start  dose  (900  mg  efficient  but  may  become
harmful)
-  Palliative therapy

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Institute of Genomic Medicine and Rare Disorders
Semmelweis University

Head of department: Prof. Dr. Mária Judit Molnár
25-29. Tömő str., Budapest, Hungary, H-1083


Tel:+36-1-459-
1483

Email: [email protected]  mmelweis-univ.hu

Criteria for the diagnosis of Amyotrophic Lateral Sclerosis
The diagnoses of ALS requires the presence of:
1.
Signs of lower motor neuron (LMN) degeneration by clinical, electrophysiological or
neuropathologic examination,
2.
Signs of upper motor neuron (UMN) degeneration by clinical examination, and
3.
Progressive spread of signs within a region or to other regions, together with the absence
of:

Electrophysiological evidence of other disease processes
that might explain the signs of LMN and/or UMN degenerations; and

Neuroimaging evidence of other disease processes that
might explain the observed clinical and electrophysiological signs.

Steps in the diagnosis of Amyotrophic Lateral Sclerosis
The diagnoses of ALS is made possible by:
4.
History, physical and appropriate neurological examinations to ascertain clinical finding
which may suggest suspected, possible, probable or definite ALS,
5.
Electrophysiological examinations to ascertain findings which confirm LMN degeneration
in clinically involved regions, identify LMN degeneration in clinically uninvolved regions
and exclude other disorders,
6.
Neuroimaging examinations to ascertain findings which may exclude other disease
processes,
7.
Clinical laboratory examinations, determined by clinical judgment, to ascertain possible
ALS-related syndromes,
8.
Neuropathologic examinations, where appropriate, to ascertain findings which may confirm
or exclude sporadic ALS, coexistent sporadic ALS, ALS-related syndromes or ALS variants,
9.
Repetition of clinical and electrophysiological examinations at least six months apart to
ascertain evidence of progression.

Supplement 1. – Criteria of diagnosis (El Escorial World Federation of Neurology)
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Institute of Genomic Medicine and Rare Disorders
Semmelweis University

Head of department: Prof. Dr. Mária Judit Molnár
25-29. Tömő str., Budapest, Hungary, H-1083


Tel:+36-1-459-
1483

Email: [email protected]  mmelweis-univ.hu

Abbreviations: UMN, upper motor neuron; LMN, lower motor neuron; ALS, amyotrophic lateral
sclerosis.

Supplement 2: Differential diagnosis of ALS

References
Joyce NC, Carter GT. Electrodiagnosis in Amyotrophic Lateral Sclerosis. PM & R : the journal of
injury, function, and rehabilitation. 2013;5(5 0):S89-S95. doi:10.1016/j.pmrj.2013.03.020.
Manage ALS from the beginning (AAN Guideline)

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