1/42. A SOD1 gene mutation in a patient with slowly progressing familial ALS.We report a new missense mutation (Gly12Arg) [corrected] in exon 1 of the Cu/Zn superoxide dismutase (SOD1) gene in a 67-year-old patient with familial ALS (FALS). The clinical course showed an unusually slow progression. The enzymatic activity of the mutated SOD1 was 80% of normal. At the molecular level, the Gly12Arg [corrected] mutation occurs in a region outside the active site and may lead to local distortion strain in the protein structure.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/42. Presentation of ALS to the otolaryngologist/head and neck surgeon: getting to the neurologist.patients with early symptoms of bulbar amyotrophic lateral sclerosis (ALS) are usually referred to the otolaryngologist without a diagnosis. Careful examination of the speech quality and a physical exam, including the vocal cords, should be undertaken. The emotional state of the patient should be considered, and a diagnosis should not be offered before a neurologic consultation has been obtained. patients with late symptoms of bulbar ALS almost always present with both significant speech and swallowing abnormalities. Evaluation can be difficult because many abnormalities are found on examination. Advanced progression of symptoms is a clear indication for rapid referral to a neurologist if a diagnosis has not already been made. Supportive and symptomatic care should be offered to the patient immediately. The University of washington Neuromuscular Clinic for speech and Swallowing Disorders has seen 600 new neurologic patients since 1986, 211 of whom were ALS patients. The introduction of percutaneous gastrostomy has greatly changed the management of ALS patients, and 75 patients have undergone this procedure (32% because of inadequate swallowing, 68% for declining vital capacity). Medical management to improve symptoms may be indicated before surgery. Surgical options for patients with late salivary presentation are uncommon and include removal of the submaxillary glands, tracheostomy, and laryngeal or salivary diversion procedures. laryngectomy or laryngeal diversion procedures are only very rarely indicated. Although tracheostomy usually interferes with swallowing and worsens aspiration, it may rarely be indicated in patients with late airway presentation for glottic narrowing or artificial respiratory support. Symptomatic management of patients with bulbar ALS is usually best undertaken by a multidisciplinary clinic that can provide a physically and psychologically supportive environment.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
3/42. Numerous conglomerate inclusions in slowly progressive familial amyotrophic lateral sclerosis with posterior column involvement.A 59-year-old woman with slow progression of the loss of motor function and predominant lower motor manifestation during a 14-year period showed familial amyotrophic lateral sclerosis (fALS) with posterior column involvement, neuropathologically. Conglomerate inclusions (CIs) were observed in the remaining neurons in various areas, including the spinal anterior horn, posterior horn, Clark's column, accessory cuneate nucleus, tegmental reticular formation, motor nucleus of the trigeminal nerve, nucleus of the facial nerve, hypoglossal nucleus, medial nucleus of the thalamus, dentate nucleus, and motor cortex (Betz cells). Immunohistochemically, it was newly identified that the CIs showed marked immunoreactions with antibodies to phosphorylated and non-phosphorylated neurofilaments and to 64, 120, and 200 kD neurofilaments. The CIs were partially immunoreactive with the anti-ubiquitin antibody, although they reacted only weakly (or not at all) with anti-Cu/Zn superoxide dismutase (SOD1) antibody. Ultrastructurally, the CIs were comprised of neurofilaments. These data suggest that this case might have been different from an example of fALS with Ile 113 Thr mutation in the SOD1 gene.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
4/42. Coexistence of dominant and recessive familial amyotrophic lateral sclerosis with the D90A Cu,Zn superoxide dismutase mutation within the same country.The Cu,Zn superoxide dismutase (Cu,Zn SOD) mutations described in amyotrophic lateral sclerosis (ALS) have, for the most part, a dominant influence. However, while a few cases with a heterozygous D90A mutation have been described in different countries, D90A has been recently proven to be recessively inherited with a common founder effect in scandinavia. We screened French ALS families for Cu,Zn SOD mutations. The presence of the D90A allele was found in two index-cases, and their families were subsequently studied. In the first family the ALS patients were homozygotes for D90A, while in the second, all ALS patients were heterozygotes. In both families the disease was found to initially involve the lower limbs with slower progression than in sporadic cases, and frequent atypical signs such as paresthesia and urgency of micturition. We determined the D90A allele frequency in controls (n = 200) and sporadic ALS patients (n = 408). No D90A allele was found. This is the first report of coexistence of dominant and recessive families with the D90A Cu,Zn SOD mutation within the same country.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
5/42. Sporadic ALS associated with the D90A Cu,Zn superoxide dismutase mutation in russia.Twenty blood samples from Russian patients (moscow) with idiopathic motor neurone disease were analysed for mutations in the Cu,Zn superoxide dismutase (Cu,Zn SOD) gene. Two patients (10%) with the amyotrophic lateral sclerosis (ALS) form of the disease were found to have a disease-related mutation. One patient appears to have autosomal recessive adult-onset ALS associated with homozygosity for D90A and presents the characteristic phenotype of very slowly ascending paresis with both lower and upper motor neurone signs. Another patient, heterozygous for D90A, presents ALS with lumbar onset and rapid progression. This is the first report of a Cu,Zn SOD mutation in ALS in russia.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
6/42. Familial amyotrophic lateral sclerosis with a novel Leu126Ser mutation in the copper/zinc superoxide dismutase gene showing mild clinical features and lewy body-like hyaline inclusions.BACKGROUND: Mutations in the SOD1 gene are responsible for approximately 25% of all familial amyotrophic lateral sclerosis (ALS) cases. However, the correlation between the clinical and pathological features and the various SOD1 gene mutations has not been well characterized. OBJECTIVES: To screen the SOD1 gene in search of potential mutations and to obtain clinical and pathological data for 2 Japanese families with ALS. DESIGN: Clinical histories and neurological findings, gross and microscopic pathological features, and dna analysis of the SOD1 gene. RESULTS: The 2 families with ALS showed a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation TTG to TCG, causing substitution of leucine for serine at codon 126 (Leu126Ser) in exon 5. Clinically, patients showed slower disease progression and lack of upper motor neuron signs. Neuropathologically, the autopsied patient showed the form of familial ALS with posterior column involvement, and the pontocerebellar tract and the dentate nuclei of the cerebellum were also involved. Furthermore, abundant Lewy body-like hyaline inclusions were observed in the affected motor and nonmotor neurons. CONCLUSIONS: Familial ALS with a novel Leu126Ser mutation in the SOD1 gene showed mild clinical features and lack of upper motor neuron signs. We believe that Leu126Ser might be associated with the clinical features and that the mutation site in the SOD1 gene and disease duration might be associated with the formation of Lewy body-like hyaline inclusions.- - - - - - - - - - ranking = 56.790631554056keywords = disease progression, progression (Clic here for more details about this article) |
7/42. A case of amyotrophic lateral sclerosis with a very slow progression over 44 years.We report on a patient whose neurological and neurophysiological findings fulfil the El Escorial criteria for definite amyotrophic lateral sclerosis (ALS), and who is still alive 44 years after the initial diagnosis. Pertinent differential diagnoses were excluded on clinical and/or genetic grounds. Our patient has no afflicted relatives and her SOD1 testing was negative, thus allowing us to classify her form of ALS as sporadic. Informing ALS patients of the existence of documented cases with long-term survival can be a means of fostering hope when delivering the diagnosis.- - - - - - - - - - ranking = 4keywords = progression (Clic here for more details about this article) |
8/42. Hereditary pure lower motor neuron disease with adult onset and rapid progression.We describe three members each of two families presenting with a hereditary form of lower motor neuron disease with adult onset and rapid progression and compare their pathological and clinical features with hereditary lower motor neuron disease with adult onset, as described in the literature. No involvement of upper motor neurons was found either clinically or pathologically. disease progression was rapid, and the majority of patients died from respiratory failure within 1-5 years after onset of disease. On pathological examination of the spinal cord we found ballooned neurons, neuronophagia and gliosis in family A, which have been regarded as characteristic pathological features of infantile-onset spinal muscular atrophy (SMA). In family B specific neuronal changes were observed that also occur in patients with amyotrophic lateral sclerosis (ALS). An autosomal dominant mode of inheritance would seem likely in both families. In family A the pathological findings and the clinical presentation with symmetrical proximal limb weakness show similarities with autosomal dominant SMA. Based on the finding of pathological features in family B that also occur in ALS, together with the distal asymmetrical muscle weakness and bulbar signs and a high age at onset we hypothesize that the members of family B suffered from familial ALS. The disease forms in both families in our opinion further broaden the spectrum of motor neuron disease.- - - - - - - - - - ranking = 6keywords = progression (Clic here for more details about this article) |
9/42. Familial amyotrophic lateral sclerosis with a point mutation (G37R) of the superoxide dismutase 1 gene: a clinicopathological study.A familial amyotrophic lateral sclerosis (FALS) patient with G37R mutation of superoxide dismutase 1 (SOD1) gene revealed an early onset and relatively slow progression. Neuropathological examination of this patient showed widespread neuronal degeneration extending to overall length of the spinal cord and the brainstem with extremely rare Lewy body-like inclusions (LBI), while there were no vacuoles in neurons, a characteristic feature in transgenic mice expressing G37R SOD1 mutation.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
10/42. Mitochondriopathy mimicking amyotrophic lateral sclerosis.BACKGROUND: Mitochondriopathy has been rarely reported to imitate motor neuron disease. review SUMMARY: A 57-year-old, 157-cm-tall woman with clinical and electrophysiological features of motor neuron disease since 1993 is reported. She also had increased liver function parameters, hypothyroidism, and sinus tachycardia. Because her mother and sister had both died from assumed amyotrophic lateral sclerosis, familial ALS was diagnosed. On reevaluation, screening for superoxide-dismutase gene mutations was negative, but lactate stress testing was abnormal and muscle biopsy revealed patchy COX deficiency and abnormal mitochondria. Analysis of the muscle mtDNA revealed substitutions in the isoleucine tRNA, in the ATPase-6, and in the cytochrome-b gene, respectively. Based on these data, the diagnosis of ALS was changed to mitochondriopathy. CONCLUSIONS: Mitochondriopathy may mimic ALS, phenotypically and electrophysiologically. In patients with an ALS phenotype, slow progression, and multisystem involvement, mitochondriopathy should be considered a diagnostic possibility.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
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