L-tryptophan: a rational anti-depressant and a natural hypnotic?

L-tryptophan is an essential amino acid which is the metabolic precursor of serotonin. Because of the evidence that serotonin deficiency may be an aetiological factor in some sorts of affective disorder and that serotonin is important in the biochemistry of sleep, L-tryptophan has been suggested as a "rational" anti-depressant and as a "natural" hypnotic. This paper reviews the biochemistry and pharmacology of L-tryptophan as well as the literature of the clinical trials that have been conducted with it and suggests that, by itself, L-tryptophan may be useful in mild cases of depression accompanied by endogenous features and cases of bipolar disorder resistant to standard treatments. It also potentiates the monoamine oxidase inhibitors and possibly the serotonergic tricyclic drugs. L-tryptophan may improve the depressed mood of Parkinsonian patients and has a clinically useful hypnotic action. There is evidence it may be useful in organic mental disorders induced by levodopa. Dosage schedules, contraindications and complications are discussed.     

Neurological impairment in α-mannosidosis: a longitudinal clinical and MRI study of a brother and sister

Neurological development over a period of 25 years and MRI findings are reported in two members of the same family affected by mannosidosis type II. Progressive axial and appendicular cerebellar syndrome, moderate hearing loss and deterioration of gait were present in both patients. Neuropsychological deficiency was severe, but progression over the years was not observed except in the woman’s speech capacity. Neither of the patients showed clinical improvement. A progressive corticosubcortical atrophy stands out in the brain neuroimaging studies, especially at the vermian cerebellar level. The osseous cranial deformities are very characteristic and include brachycephaly, thickening of the calvaria at the expense of the diploe, and poor pneumatization of the sphenoid. Neither of our cases showed an empty sella turcica. Received: 8 February 1999     

Recurrent hyper- and hyposomnia: a new diagnostic entity? Polysomnographic findings and a 30-year follow-up

OBJECTIVES: This study reports on the sleep evaluation and follow-up of a professional woman who, in her 30s and 40s, had a decade of severe episodic fluctuations in the length of her sleep (12 vs. 4 h). BACKGROUND: Severe psychogenic fluctuations in the duration of sleep have not previously been described except in bipolar disorders. METHODS: Psychological and medical history and a total of 29 polysomnogram nights are presented, as well as a 30-year follow-up interview. RESULTS: Long sleep episodes (>10 h) were characterized by excessive stage 1 sleep and a stage we called 'very light sleep' (over 50% alpha waves mixed with 5-10% delta waves). Long sleeps were also associated with hyperphagia and hypersexuality. Short sleeps (<4 h) emphasized delta and REM sleep. Sleep normalized spontaneously after about a decade of severe fluctuations. CONCLUSIONS: In this patient, the recurrent hypersomnia/hyposomnia episodes may have been based mainly on psychiatric factors.     

XY sex reversal and a nonprogressive neurologic disorder: a new syndrome?

We report a patient with a unique combination of clinical findings: XY sex reversal, spastic paraplegia, mental retardation, dysmorphism, and infantile-onset olivopontocerebellar hypoplasia. The phenotype of our patient did not coincide with any of the described forms of XY reversal syndromes, hereditary or sporadic spastic paraplegias, or congenital or infantile-onset cerebellar or olivopontocerebellar atrophies or hypoplasias. The disorder of this patient likely represents a genetic condition with pleiotropic effects on brain development and sex determination and adds further evidence for the heterogeneity of spastic paraplegia/infantile olivopontocerebellar hypoplasia syndromes and sex reversal syndromes.     

Schizophrenia and beta-thalassemia: a genetic link?

This report of two cases in which schizophrenia and beta-thalassemia occurred simultaneously in several family members may suggest that a genetic link exists between these two disorders. A known genetic disease (beta-thalassemia) could help confirm the presence, on the short arm of chromosome 11, of a genetic susceptibility factor for schizophrenia.     

Dizziness and migraine: a causal relationship?

Both migraine and dizziness are very frequent complaints, but the comorbidity of the two disorders is higher than it might be expected to be on the basis of chance alone. This implies a possible causal relationship, but definite diagnostic criteria for migraine-related vertigo are still lacking. Very recent attempts in this direction have shown that migraine may be the third leading cause of vertigo and that migraine-related vertigo may be effectively treated. A review of the literature on this topic, which includes some preliminary data of our own, demonstrates the difficulty in pinpointing migraine-associated vertigo as a clearly-defined entity. However, there is a measure of agreement on a few points: the spells of vertigo occur in patients who habitually suffer from motion sickness, and who have a history of migraine, either without or with aura; the delay between migraine and vertigo onset may be several years; migraine-related vertigo may be described as rotatory and/or as a feeling of unsteadiness, and single spells can occur without any other accompanying symptoms, however, when spells do occur in association with headache, they usually precede it. The vertigo duration may be shorter or longer than that of the migraine aura since it ranges from a few seconds to a continuous condition of unsteadiness.     

RCVS and TGA: a common pathophysiology?

Journal of Neurology -     

Myoclonus and neurodegenerative disease--what's in a name?

Myoclonus is a clinical symptom (or sign) defined as sudden, brief, shock-like, involuntary movements caused by muscular contractions or inhibitions. It may be classified by examination findings, etiology, or physiological characteristics. The main physiological categories for myocolonus are cortical, cortical-subcortical, subcortical, segmental, and peripheral. Neurodegenerative syndromes are potential causes of symptomatic myoclonus. Such syndromes include multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17, Huntington's disease, dentato-rubro-pallido-luysian atrophy, Alzheimer's disease, and Parkinson's disease, and other Lewy body disorders. Each neurodegenerative syndrome can have overlapping as well as distinctive clinical neurophysiological properties. However, claims of differentiating between neurodegenerative disorders by using the presence or absence of small amplitude distal action myclonus appear unwarranted. When the myoclonus is small and repetitive, it may not be possible to distinguish it from tremor by phenotypic appearance alone. In this case, clinical neurophysiological offers an opportunity to provide greater differentiation of the phenomenon. More study of the myoclonus in neurodegenerative disease will lead to a better understanding of the processes that cause phenotypic variability among these disorders.     

Molecular engineering of a secreted, highly homogeneous, and neurotoxic aβ dimer

Aβ oligomers play a key role in the pathophysiology of Alzheimer's disease. Research into structure-function relationships of Aβ oligomers has been hampered by the lack of large amounts of homogeneous and stable material. Using computational chemistry, we designed conservative cysteine substitutions in Aβ aiming at accelerating and stabilizing assembly of Aβ dimers by an intermolecular disulfide bond without changing its folding. Molecular dynamics simulations suggested that mutants AβS8C and AβM35C exhibited structural properties similar to those of Aβ wildtype dimers. Full length, mutant APP was stably expressed in transfected cell lines to study assembly of Aβ oligomers in the physiological, secretory pathway and to avoid artifacts resulting from simultaneous in vitro oxidation and aggregation. Biochemical and neurophysiological analysis of supernatants indicated that AβS8C generated an exclusive, homogeneous, and neurotoxic dimer, whereas AβM35C assembled into dimers, tetramers, and higher oligomers. Thus, molecular engineering enabled generation of bioactive, homogeneous, and correctly processed Aβ dimers in vivo.