Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In amyotrophic lateral sclerosis (ALS), muscles with preserved strength can have fasciculation potentials (FPs) as the only abnormality. The FPs in strong muscles are predominantly simple and stable, and can often be recruited by a slight voluntary contraction. In weak and atrophic muscles, the FPs are generally complex and unstable, tend to have a slower firing rate and are not recruited by voluntary contraction. Macro-electromyography studies suggest that these FPs are part of a more complex motor unit, as opposed to simple FPs which can represent all the motor unit. FPs driven by transcranial magnetic stimulation (TMS) were observed in 13 ALS patients. TMS-driven fasciculations had a simple morphology and were stable. Complex potentials were never cortically driven. These observations strengthen the conviction that fasciculations in ALS can have different origins. Simple, stable FPs arise proximally and are probably related to excitotoxicity phenomena, while complex, unstable FPs are most likely to originate in distal axonal sprouts that are associated with the reinnervation process. Some ALS patients with fatigue and mild weakness can have profuse fasciculations at an early phase in the evolution of the disease. Patients with denervation localized in one region and diffuse FPs should be strongly suspected of having ALS. With this strategy it should be possible to shorten the diagnosis time.
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PMID:Pathophysiological significance of fasciculations in the early diagnosis of ALS. 1146 25

The challenge of identifying patients at the earliest stage of disease has highlighted the role of subtle markers of clinical pathology. Electrophysiological changes usually precede evidence of clinical weakness and have, therefore, been implicated. Specifically, the onset of fasciculations, particularly those widespread in distribution, in the absence of fibrillation potentials, have been suggested as an early indicator of motor neuron disease. Several cases will be presented here to highlight instances where diffuse fasciculations were not enough to accurately implicate the current diagnostic criteria for amyotrophic lateral sclerosis (ALS). In two instances, alternative diagnoses were eventually supported. If the purpose of early diagnosis is to lead to early treatment with experimental therapy, we must be certain that we study as homogenous a population of patients as possible. Fasciculations by themselves are not enough to implicate early diagnosis; disease progression is probably the single most important historical characteristic for diagnosis. Signs of active denervation (i.e. fibrillation potentials) are critical. Chronic weakness should be proportional to either atrophy or upper motor neuron signs in the affected muscle. This should be true for both early and late recognition of the disease.
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PMID:Fasciculations without fibrillations: the dilemma of early diagnosis. 1146 27

We describe a patient with amyotrophic lateral sclerosis with dementia (ALS-D) displaying a long clinical course. A 68-year-old Japanese male with no family history of note was admitted complaining of severe dysarthria and dysphagia. At 63 years old, Pick's disease was diagnosed on the basis of abnormal behavior, such as "Denkfaulheit" and moria, and temporal lobe atrophy observed on magnetic resonance imaging (MRI). Five years after onset, dysarthria and dysphagia emerged, and gradually worsened. On admission, muscular weakness of the upper extremities, fasciculation, and exaggerated tendon stretch reflexes were noted. Needle electromyography performed on the left upper and lower extremities revealed neurogenic pattern changes. Based on these findings and clinical course, ALS-D was diagnosed. Due to severe bulbar palsy, verbal communication was impossible. However, neither specific symptoms of dementia nor abnormal behavior was demonstrated, although this latter had been observed 5 years ago, with only short-term memory impairment apparent. MRI disclosed severe knife-edge atrophy of bilateral temporal lobes, most prominently in the anterior regions. SPECT images revealed decreased uptake of tracer in bilateral inferior temporal lobes, predominantly on the left side. The patient died suddenly 4 months after admission, and post-mortem examination was not conducted. Total clinical course was about 8 years. Several cases of ALS-D have displayed similar clinical courses to the presented case. Some of these would also have initially been diagnosed as Pick's disease. We speculate that cases displaying psychiatric symptoms for several years and initially diagnosed as Pick's disease may finally be diagnosed as ALS-D upon the eventual emergence of motor symptoms(bulbar palsy).
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PMID:[A case of amyotrophic lateral sclerosis with dementia presenting long clinical course]. 1268 97

The anterior horn cell diseases, with the exception of polio, are progressive degenerative diseases of the motor neurons. These disorders include SMA types I to III in children and familial and sporadic ALS and its variants (PMA, PLS, and PBP), Kennedy's disease, and SMA type IV in adults. The electrodiagnostic study is a crucial step in the diagnostic process for all of these disorders. In general, motor NCS may be normal or reveal low CMAP amplitudes with relatively normal conduction velocities. Sensory NCS, except in the case of Kennedy's disease, are normal. The NEE is notable for the often abundant presence of abnormal spontaneous activity, including fibrillation potentials and positive sharp waves, fasciculation potentials, and complex repetitive discharges. Motor unit morphology is abnormal, with polyphasic motor units and large amplitude and duration MUAPs when the disease is slowly progressive. Recruitment in affected muscles is reduced with abnormally rapidly firing motor units. To diagnose a widespread disorder of the motor neurons, abnormalities must be present in multiple muscles with different nerve root and peripheral nerve innervation in multiple limbs. The Lambert Criteria and the El Escorial Criteria are the two most widely accepted sets of electrodiagnostic criteria for ALS. The electrodiagnostic diagnosis must be supported by appropriate history and physical examination findings and the exclusion, via neuroimaging and laboratory testing, of other diseases that may mimic a generalized disorder of the motor neurons.
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PMID:Amyotrophic lateral sclerosis and other motor neuron diseases. 1279 19

In this case study, we describe the symptoms, neurological examination, and pathology of a woman with amyotrophic lateral sclerosis (ALS). ALS is a rare disorder leading to degeneration of the voluntary motor system and death in, on average, 3 to 4 years. The loss of motor neurons in the brain and spinal cord causes the progressive symptoms of muscular weakness, atrophy, fasciculation (muscle twitching), spasticity, and hyperreflexia. Signs of disease in both upper and lower motor neurons are required for a definitive clinical diagnosis. Pathology shows degeneration of the lateral corticospinal tracts, loss of motor neurons and astrogliosis in the brain and brain stem, and neuronal inclusions. This case was marked by the onset of weakness and muscle atrophy in the hand, which spread to involve contiguous muscle segments. Cognition, the extraocular muscles, and the urinary sphincters were spared. Respiratory muscle weakness was a late manifestation.
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PMID:Amyotrophic lateral sclerosis. 1295 82

We report a case displaying upper motor sign, parkinsonism, and behavioral abnormality, with marked degeneration of the precentral cortex, neostriatum and frontotemporal lobes, as well as ubiquitinated neuronal inclusions. The patient was a 66-year-old male at the time of death. At age 57, he noticed progressive difficulties in speaking and swallowing. At age 60, he was severely anarthric and displayed emotional lability and incontinence. Neurologically, very poor movement of tongue was observed, but without atrophy or fasciculation. Deep tendon reflexes were hyperactive. Grasp reflex and snout reflex were also positive. Needle electromyography revealed no abnormalities. A diagnosis of primary lateral sclerosis and character change was made. At age 62, he developed bradykinesia and rigidity of the neck and all extremities. Treatment with carbidopa-levodopa was initiated, but resulted in minimal improvement. At age 65, he was bed-ridden, and had repeated occurrences of aspiration pneumonia; he died of pneumonia. Neuropathological examination revealed marked atrophy of the frontal and temporal lobes with Betz cells completely absent and moderate atrophy of the neostriatum. The spinal cord and nerve roots appeared normal. Immunohistochemically, ubiquitin-positive but tau-negative intraneuronal inclusions were found in the frontal and temporal cortices, including the precentral cortex and the hippocampal dentate gyrus, and the neostriatum. This case could be included with inclusion-associated disorders such as frontotemporal dementia or amyotrophic lateral sclerosis with dementia, and furthermore, predominant upper motor sign and parkinsonism could represent phenotypes of clinical manifestations with such inclusions.
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PMID:Frontotemporal dementia with ubiquitinated neuronal inclusions presenting with primary lateral sclerosis and parkinsonism: clinicopathological report of an autopsy case. 1476 75

This report concerns an autopsy case of sporadic amyotrophic lateral sclerosis (ALS) clinically diagnosed as having spinal progressive muscular atrophy (SPMA). The patient was a Japanese woman without hereditary burden. She developed muscle weakness in the distal part of the right upper extremity at age 52, followed by muscle weakness in the left upper extremity and lower extremities at age 54 and 64, respectively. At age 66 she could not walk, even with assistance. Fasciculation and atrophy of the tongue appeared at age 68, followed by dysphagia and dysarthria at age 70. She died of respiratory disturbance at age 71. During the clinical course, neurological examination revealed neither Babinski sign nor hyperreflexia. No respirator administration was performed throughout the clinical course. Neuropathological examination disclosed not only neuronal loss with gliosis in the hypoglossal nucleus and anterior horns of the spinal cord, but also loss of Betz cells and degeneration of the pyramidal tract. Based on these clinicopathological findings and a literature review of sporadic autopsy cases of ALS with long clinical course (10 years or more), including four cases without pyramidal signs, we believe that sporadic ALS of long clinical course mimicking SPMA exists.
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PMID:Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy exists: additional autopsy case with a clinical course of 19 years. 1548 1

We report a family with autosomal dominant (AD) motor neuron disease. A 41-year-old man developed muscle weakness and fasciculation of the lower extremities. The weakness progressed to the upper extremities and bulbar muscles. The cerebrospinal fluid (CSF) protein level was slightly elevated. A nerve conduction study revealed reduced compound muscle action potentials, but conduction block was not observed. Electromyogram showed acute and chronic neurogenic changes. He was treated with intravenous immunoglobulin (IVIg) and methylprednisolone pulse therapy, but his condition rapidly deteriorated. He developed respiratory failure necessitating artificial ventilation within three months after the onset of the disease. His father developed muscle weakness and atrophy of the upper extremities at age 70, and his cousin developed muscle weakness of the legs at age 41. Their conditions rapidly progressed to quadriplegia. CSF and electrophysiological findings were similar to those of the proband. Treatments by steroid pulse therapy, IVIg, and plasmapheresis were not effective. The father and cousin also required artificial ventilation within 3-4 months from the onset of symptoms, and became locked-in state. Autosomal dominant amyotrophic lateral sclerosis (AD-ALS) was considered, but SOD1 gene mutation was not detected. The present pedigree may have familial ALS caused by a gene mutation other than SOD1.
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PMID:[Familial amyotrophic lateral sclerosis with rapid progression]. 1636 40

A 71-year-old woman with a family history of amyotrophic lateral sclerosis (ALS) was investigated for symmetrical, proximal limb and abdominal muscle weakness. Initial examination showed mild proximal muscle weakness in the arms and legs, slightly elevated serum creatine kinase (CK) level, and normal electromyographic (EMG) findings. A myopathy was the presumed diagnosis. Over the next year, weakness became severe and tendon reflexes became unelicitable; no upper motor signs were present. EMG then showed acute and chronic denervation and a muscle biopsy showed target fibers and grouped atrophy. DNA analysis revealed a G72C CuZn-superoxide dismutase (SOD1) mutation. Fasciculations were absent throughout the disease. The patient died 53 months after symptom onset and autopsy revealed loss of lower motor neurons (LMN) and SOD1-positive inclusions. This case expands the phenotypic spectrum of ALS associated with SOD1 mutations to include presenting features that mimic a myopathy.
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PMID:Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation mimicking a myopathy. 1643 43

Fasciculations are a characteristic feature of amyotrophic lateral sclerosis (ALS), and can arise proximally or distally in the motor neuron, indicating a widespread disturbance in membrane excitability. Previous studies of axonal excitability properties (i.e. threshold electrotonus, strength-duration time constant) have suggested respectively that change in potassium or sodium channels may be involved. To reinvestigate these changes and explore their correlation with disease stage, multiple axonal excitability properties (threshold electrotonus, strength-duration time constant, recovery cycle and current-threshold relationship) were measured for the median nerve at the wrist in 58 ALS patients, and compared with 25 age-matched controls. In ALS, there were greater changes in depolarizing threshold electrotonus (i.e. less accommodation) (P < 0.001) and greater supernormality in the recovery cycles (P < 0.001). These abnormalities were more prominent in patients with moderately reduced CMAP (1-5 mV). Modelling the excitability changes in this group supported the hypothesis that axonal potassium conductances are reduced, resulting in increased supernormality despite membrane depolarization. The tendency for strength-duration time constant to be prolonged in ALS was only significant for patients with normal CMAP amplitude (>5 mV). Patients with severely reduced CMAP (<1 mV) alone showed reduced threshold changes to hyperpolarizing current. These results suggest a changing pattern of abnormal membrane properties with disease progression. First, persistent Na+ conductance increases, possibly associated with collateral sprouting, and then K(+) conductances decline. Both changes cause axonal hyperexcitability, and may contribute to the generation of fasciculations. These serial changes in axonal properties could provide insights into the pathophysiology of ALS, and implications for future therapeutic options.
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PMID:Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage. 1646 88


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