M.I. Botez

Reversible chronic cerebellar ataxia after phenytoin intoxication Possible role of cerebellum in cognitive thought

Reversible chronic cerebellar ataxia followed phenytoin treatment in two epileptic women. Cerebellar ataxia in both patients and axonal polyneuropathy in one patient were improved after administration of thiamine alone or with folate. In one patient, some specific behavioral functions improved. However, recovery could have been spontaneous.

Folate-responsive neurological and mental disorders: Report of 16 cases

Two groups of patients with folic acid responsive neurological and psychiatric disorders are reported. The first group (7 patients) had well-established acquired folate deficiency due either to defective absorption (4 cases with atrophy of jejunal mucosa) or to a deficient diet (3 cases). One patient had a subacute combined degeneration of the spinal cord while others were depressed and had weight loss, permanent muscular and intellectual fatigue, restless legs syndrome, depressed ankle jerks, diminution of the sense of vibration in the knees and a stocking-type tactile hypoesthesia. The second group (9 patients) comprised idiopathic cases of folic acid deficiency. Their main subjective complaints were chronic fatigability and familial restless legs syndrome. The neurological findings were similar to those of the patients with acquired disorders. Neuropsychological testing procedures revealed an abnormal intellectual functioning in all 16 patients. Abnormal patterns of radionuclide cisternograms and computerized transaxial tomography (CTT) were found in 11 patients. After 6-12 months of folic acid therapy a striking improvement regarding their intellectual functioning was noticed: the IQ, Kohs Block Design and Category tests were significantly improved. The correlation of neuropsychological findings with CTT and radionuclide cisternograms led to the conclusion that chronic folate deficiency could induce cerebral atrophy.

Cerebellar atrophy in epileptic patients.

High-resolution CT scans of the brain and posterior fossa were performed on 106 phenytoin (PHT)-treated epileptics, 28 de novo epileptics and 43 control subjects. A higher incidence of cerebellar and brainstem (CBS) atrophy was observed in chronic PHT- or PHT+ phenobarbital-treated epileptics compared to the two other groups. Some control subjects and de novo epileptics presented mild CBS atrophy, whereas moderate to severe atrophy was noted exclusively in chronically-treated patients. In attempting to delineate the etiology of CBS atrophy, epileptic patients were divided in three groups: 55 subjects with normal CT scans, 30 with both cerebral and CBS atrophy, and 49 with pure CBS atrophy. Their ages, length of illness, number of generalized seizures, number of other seizures, and amount of PHT received during their lifetime were assessed. Statistical analysis revealed that posterior fossa atrophy in epileptics was significantly correlated with both the length of the illness and the amount of PHT ingested during the patients lifetime. The number of seizures appears to not be related to CBS atrophy.

Defective Revisualization: Dissociation Between Cognitive and Imagistic Thought Case Report and Short Review of the Literature

A 38-year-old shifted-sinistral patient displayed a definite deficit in visual imagery accompanied by defective dreaming capacity, loss of hypnagogic imagery, some defects in topographical memory, a mild unilateral right spatial neglect and mild difficulties in right-left orientation on the examiners body. CT-scan and NMR studies showed evidence of an inborn hypoplasia of the right hemisphere and a stretched corpus callosum in its posterior and superior part. The vicarious compensatory action of the cognitive-verbal function of the defect of visual imagery was obvious. It is concluded that: there are various forms of visual imagery deficits: some are pure whereas in the great majority of reported cases the loss of visual imagery is associated to different forms of visual agnosia; the brain mechanisms underlying cognitive thought and imagistic thought could be obviously dissociated.

Occult Disorders of the Cerebrospinal Fluid Dynamics

Workable criteria are proposed that allow early recognition of mild forms of occult hydrocephalus and correlated disorders. Two groups of patients are analyzed, i.e. a group of twelve mild but classical forms of low-pressure hydrocephalus and another group of 20 patients with atypical clinical forms of disorders of the CSF dynamics. Two control groups are presented for neuropsychological comparison purposes: a normal control group of 50 subjects and a small group of three commissurotomized subjects. Patients with an overt demential syndrome due to a normotensive hydrocephalus syndrome were excluded from the study. The authors found the grasp reflex of the foot and the tonic foot response to be present in all cases with the Hakim and Adams triad. In such cases the grasp reflex is usually accompanied by the forward groping of the foot and the grasp reflex of the hand. The most helpful and useful clinical findings for an early diagnosis are the presence of the grasp reflex of the foot and of the tonic foot response of the sole in such organic brain-damaged patients with (1) a normal routine neurological examination and (2) an apparently normal mental status and even with a rather normal IQ. These reflexes are usually the single objective clinical findings in all forms of mild and occult disorders of the CSF dynamics, i.e., low-pressure hydrocephalus syndromes, cerebral atrophies and mixed forms cases. The next step for the diagnosis consists in a conventional IQ evaluation and a battery of tests exploring more specifically the sensorimotor integration, i.e. bimanual vs. unimanual activity, the Kohs block design test and part of the Halstead-Reitan neuropsychological test battery. In such patients there is a striking dissociation between a normal or rather normal IQ on the one hand and the results of the neuropsychological evaluation with the Kohs and Reitan tests on the other. The clinical and neuropsychological testings are then followed by isotope cisternography, PEG and EMI-Scan which confirm the presence of the organic brain damage. The recognition of such conditions is of great practical importance because it allows an early diagnosis of the brain damages. Some preliminary data regarding the medical treatment - acetazolamide - are shortly reviewed.

Folic Acid Absorption Test in Various Clinical Conditions

The folic acid absorption test (FAAT) has carried out in 18 normal control subjects; 8 patients with proven atrophy of the jejunal mucosa; 7 patients with gastric ulcus; 17 patients with reactive hypoglycemia; 13 patients with diabetes mellitus, and, finally, 9 epileptic patients treated with diphenylhydantoin (DPH). The most striking fact in this study is the difference between the FAAT in normal subjects versus patients with atrophy of the jejunal mucosa, reactive hypoglycemia and DPH consumption. On the other hand there were no significant differences in folate absorption between controls and diabetic patients.

Cerebrospinal fluid and blood thiamine concentrations in phenytoin-treated epileptics.

Thiamine and folate levels in blood and cerebrospinal fluid (CSF) were determined by microbiological assays in 23 control subjects and 11 phenytoin-treated epileptics. There was no significant difference between the two groups for serum and CSF folate levels. There was, however, a statistically significant difference between the groups for both whole blood thiamine and CSF thiamine levels. Epileptic patients being treated with phenytoin had lower values than control subjects.

Relapsing Neuropathy, Cerebral Atrophy and Folate Deficiency

The case of a 48-year-old woman with a relapsing radial palsy which followed diarrheic episodes is reported. She had low folate concentrations in serum and cerebrospinal fluid, as well as low and borderline values of cerebrospinal fluid and erythrocyte folates. She had chronic gastrointestinal disease with edema of jejunal mucosa. The patient had some degree of cerebral atrophy. The effect of folate therapy on the neuropathy was spectacular. A beneficial effect of the therapy has been observed on both EEG tracings and neuropsychological performances after 6 months of treatment.

Dietary folic acid and the activity of brain cholinergic and gamma-aminobutyric acid (GABA) enzymes.

Charles River CD male rats were randomly divided into 3 groups of five each and placed on folate deficient, folate excess, and control diets respectively. glutamate decarboxylase GAD gamma-amino-butyrate aminotransferase (GABA-T), choline acetltransferase (ChAc), and acetylcholinesterase (AChE) were assayed in the rat brains after 6 weeks of dietary treatment. Neither folate deficiency nor folate supplementation influenced the enzymes associated with GABA and acetylcholine metabolism.