ABSTRACT
METHOD: The activity and amount of SOD1 in erythrocyte lysates and the plasma amino acid content were evaluated in four familial ALS patients bearing the L84F SOD1 mutation (fALS), in an asymptomatic family member with the mutation (L84F(5)), in sporadic ALS patients (sALS) and controls. Three of the fALS patients and the L84F(5) subject were tested once a year for three consecutive years. RESULTS: At the first evaluation SOD1 activity was similar in controls, sALS and fALS; the amount of SOD1 protein was lower (P < 0.01) in fALS. In the subsequent 2 years, 34% and 52% decrease of SOD1 activity was recorded in fALS patients. The plasma amino acid pattern did not differ between controls and sALS, whereas fALS patients displayed high levels of plasma aspartate and glutamate. Aspartate was in the normal range but glutamate was still elevated in the subsequent evaluations. The L84F(5) subject had remarkably low levels of aspartate, glutamate and branched-chain amino acids. CONCLUSIONS: The method of measuring mutant SOD1 amount is indirect but the results are indicative of a reduction of mutant SOD1 taking place during fast-worsening phases of the disease. Since the disease onset of fALS patients is 42.8 +/- 11.3 years and the L84F(5) family member is asymptomatic at the age of 66, low levels of excitotoxic and branched-chain amino acids in plasma may constitute a protective factor against disease development.
Subject(s)
Amino Acids/blood , Amyotrophic Lateral Sclerosis/enzymology , Amyotrophic Lateral Sclerosis/genetics , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Amyotrophic Lateral Sclerosis/blood , Disease Progression , Erythrocytes/enzymology , Follow-Up Studies , Humans , Male , Middle Aged , Mutation , Superoxide Dismutase-1ABSTRACT
We report the difference existing between two clinical syndromes: Spiller's syndrome is caused by a complete involvement of the medial hemimedulla, while Déjérine's syndrome is determined by lesions restricted to the anterior portion of the medial hemimedulla and is characterized by hypoglossal nerve palsy and contralateral hemiparesis.
Subject(s)
Brain Diseases/pathology , Hypoglossal Nerve Diseases/pathology , Medulla Oblongata/pathology , Adult , Brain Diseases/classification , Brain Diseases/history , Diagnosis, Differential , History, 19th Century , History, 20th Century , Humans , Hypoglossal Nerve Diseases/classification , Hypoglossal Nerve Diseases/history , Male , Neurology/history , Paresis/classification , Paresis/history , Paresis/pathology , SyndromeABSTRACT
The authors report on an Italian family with eight affected members who show autosomal dominant migraine with prolonged visual, sensory, motor, and aphasic aura. These symptoms are associated with white matter abnormalities on brain MRI. All living affected members carry a Notch3 mutation (Arg153Cys) previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). White matter abnormalities occur in a variable percentage of the general migraine population; CADASIL should be suspected in migraineurs with prolonged atypical aura and white matter abnormalities.
Subject(s)
Chromosome Aberrations/genetics , Dementia, Multi-Infarct/genetics , Genes, Dominant/genetics , Migraine Disorders/genetics , Mutation, Missense/genetics , Proto-Oncogene Proteins/genetics , Receptors, Cell Surface , Brain/pathology , Chromosome Disorders , Dementia, Multi-Infarct/diagnosis , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Migraine Disorders/diagnosis , Pedigree , Receptor, Notch3 , Receptors, NotchABSTRACT
OBJECTIVE: To study three new apparently unrelated Italian families with ALS and several sporadic ALS patients living in the same rural area. BACKGROUND: One Italian family with ALS carrying a superoxide dismutase 1 (SOD1) gene mutation (G41S) and no regional ALS clustering has been reported in Italy. METHODS: Genetic analysis was performed by automated and manual sequencing of the SOD1 gene in 13 family members and in 6 of 10 unrelated patients with sporadic cases of ALS living in the same area. The authors also determined SOD1 activity in erythrocytes and lymphocytes. RESULTS: The three families included a total of 28 affected members distributed over six generations. Despite a wide variability in age at onset and disease duration, the clinical pattern is uniform, with onset in the lower limbs, ascending progression, and predominant lower motor neuron involvement in all subjects. Generational anticipation is evident in the last two generations. All familial ALS patients and one of the six sporadic patients carry the same L84F missense point mutation in exon 4 of the SOD1 gene. SOD1 enzyme activity and SOD1 protein levels were not decreased significantly in the L84F patients. CONCLUSION: The ALS patients carrying the L84F mutation derive from a common ancestor. This mutation is responsible for ALS clustering in the area. The L84F mutation does not modify SOD1-specific activity.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Mutation/genetics , Superoxide Dismutase/genetics , Adult , Female , Humans , Italy , Male , Middle Aged , Pedigree , Superoxide Dismutase-1Subject(s)
Mutation , PrPC Proteins/genetics , PrPSc Proteins/genetics , Prion Diseases , Prions/pathogenicity , Animals , Brain Chemistry/genetics , Humans , PrPC Proteins/metabolism , PrPSc Proteins/metabolism , Prion Diseases/diagnosis , Prion Diseases/etiology , Prion Diseases/genetics , Prion Diseases/pathology , Prion Diseases/physiopathologySubject(s)
Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/physiopathology , Facial Nerve/physiopathology , Facial Paralysis/genetics , Facial Paralysis/physiopathology , Adolescent , Blinking/physiology , Electric Stimulation , Family Health , Humans , Male , Pedigree , Phenotype , PressureABSTRACT
Various neurological disorders have been related to Streptococcus pyogenes infection. Only recently, and for the first time, it has been suggested that acute disseminated encephalitis may also complicate a streptococcal infection. The case reported in this paper seems to confirm this hypothesis.
Subject(s)
Encephalitis/pathology , Streptococcal Infections/pathology , Streptococcus pyogenes , Adolescent , Humans , MaleABSTRACT
We report the case of a 34-year old patient who first complained of fever, confusion and transient ophthalmoplegia and then developed akinetic mutism, frontal lobe, pyramidal tract and extrapyramidal signs. Clinical and electrophysiological data support a diagnosis of encephalitis lethargica. Magnetic resonance imaging showed hyperintensive lesions in various brain regions. The patient responded to corticosteroid treatment. Two years after the onset of the first clinical signs he had recovered completely and today, after 5 years, he shows no sign of disease.
