Hanan Costeff

Multiple syndromes of 3-methylglutaconic aciduria

The most common clinical syndromes associated with 3-methylglutaconic aciduria are presented. In some patients these syndromes are multisystemic, progressive disorders of unknown etiology. Tissues deriving significant energy through oxidative metabolism (notably brain and cardiac muscle) are most often affected and in some the primary defect may reside within the mitochondrial respiratory chain. Although increasing biochemical evidence suggests that 3-methylglutaconic aciduria may correlate with deranged mitochondrial energy metabolism, the biochemical origin of 3-methylglutaconic acid and the significance of its increased excretion remain unknown. This review describes these syndromes and illustrates the necessity of urinary organic acid analysis to assist in the differential diagnosis.

Evaluation of Tinel’s and Phalen’s Signs in Diagnosis of the Carpal Tunnel Syndrome

In 80 upper extremities clinically suspected of carpal tunnel syndrome, electromyography (EMG) was performed and the Phalen and Tinel signs were sought. These two signs showed relatively low sensitivity (60-67%) and specificity (59-77%) despite a statistically significant association with the EMG findings. These two signs are not reliable as clinical criteria for carpal tunnel syndrome.

Biological factors in mild mental retardation

A group of 434 children with non‐syndromic mental retardation was analysed for frequency of recorded prenatal, perinatal and infantile biological disturbances. Mildly retarded individuals of unrelated parentage, both idiopathic and familial, had a strikingly higher prevalence of recorded disturbances than did a control group of retarded individuals with consanguineous parents and of probably genetic aetiology. These disturbances were as frequent among those with mild retardation as among parallel groups with severe retardation. The most significant single disturbance among the midly retarded was a history of maternal reproductive inefficiency. These findings conflict with the view that mild retardation is predominantly ‘cultural‐familial’ and is not pathological in nature.

Pathogenic Factors in Idiopathic Mental Retardation

Pathogenic factors in à mentally retarded population were evaluated by comparing their frequency among three groups of patients: à control group with predominantly genetic retardation and consanguineous parents; à group with severe idiopathic retardation and unrelated parents; and à group with mild idiopathic retardation and unrelated parents. Seven factors were found to be significantly more common among the patients with idiopathic retardation than in the genetic control group: à history of maternal reproductive inefficiency; bleeding during pregnancy; toxemia during pregnancy; signs of perinatal stress; neonatal anoxia; neonatal jaundice; and seizures during the first year of life. à history of repeated maternal abortions was particularly associated with mild retardation, and infantile seizures were particularly associated with severe retardation. The latter association remained significant even after exclusion of all infantile spasms, neonatal seizures and symptomatic seizures.

3-METHYLGLUTACONIC ACIDURIA IN THE IRAQI-JEWISH “OPTIC ATROPHY PLUS‘ (COSTEFF) SYNDROME

Eleven new patients of Iraqi‐Jewish origin with bilateral optic atrophy, neurological abnormalities (‘optic atrophy plus’ syndrome) and 3‐methylglutaconic aciduria (type III) are described. Clinical abnormalities in decreasing order of frequency were bilateral optic atrophy, extrapyramidal signs, spasticity, ataxia, dysarthria and cognitive deficit. An association with age was found only for spasticity. Spasticity, extrapyramidal signs and optic atrophy frequently led to major disability, in contrast to ataxia, dysarthria and cognitive deficit. The combined excretion of 3‐methylglutaconic and 3‐methylglutaric acid ranged between 9 and 187mmol/mol creatinine. The primary enzymatic defect possibly may reside in the mitochondrial respiratory chain.

The Diagnostic Value of Three Common Primitive Reflexes

Systematic attempts were made to elicit the snout, palmomental and corneomandibular reflexes in 50 young patients with prolonged traumatic coma, 50 elderly hemiplegics soon after their first cerebrovascular accident and in 100 normal age-matched controls. None was found significantly more frequently alone in brain-damaged patients than in age-matched controls. Only combinations of two or three reflexes showed diagnostic value in distinguishing between neurologically damaged patients and normal age-matched controls. Only the combination of all three was completely absent in the normal controls; this combination was found in 13% of the brain-damaged subjects.

Childhood head injuries in Israel: epidemiology and outcome

Results are reported of a regional survey of hospitalized head injuries in Israeli children aged 0-7 years during the period 1970-1976. There were 370 such cases surveyed. Incidence of head injury requiring hospitalization was 1.71/1000 per year. Follow-up examination 4-10 years after injury was achieved in 50 per cent of the cases. Late seizures and focal neurological deficit were rare, while school failure and various neuropsychiatric symptoms were common. Prevalence of seizures and new nervous habits was significantly related to severity of injury, while the prevalence of fears, nightmares, dizziness and school failure was not.

CT findings in persistent vegetative state following blunt traumatic brain injury.

The use of linear measurements in the analysis of CT scans of TBI patients was found to contribute to the understanding of brain damage and were correlated with outcome in severe traumatic close brain injured patients. The purpose of the present study was to analyse the data obtained by the linear measurements on CT studies of TBI patients who remained in persistent vegetative state following blunt head trauma. All 27 patients included in the study were reported to be neurologically normal prior to injury. Thirteen patients, 11 remaining in persistent vegetative state (responsive but unaware) and two who died, constituted the worst outcome group. Fourteen patients who regained consciousness, underwent multidisciplinary evaluation when their recovery reached a plateau and were ranked according to severity of residual symptoms and outcome. The degree of correlation with the overall vocational outcome parameter with the various radiological indices was calculated as the Spearman rank correlation coefficient, with correction for tied scores. Fishers z transformation was used to combine results with those of our previous analysis. Three radiological parameters showed a statistically significant correlation with clinical outcome. These were the right and left septum-caudate distance and the cerebroventricular index 2; these showed Spearman rank coefficients of 0.52, 0.45 and 0.48; with two-tailed p-values under 0.01, 0.02 and 0.01 respectively. The width of the third ventricle suggested correlation with the clinical scoring. The findings of the present study point to the importance of loss of deep gray matter of the caudate nuclei and widening of the adjacent part of the lateral ventricles in catastrophic brain injury. This finding may highlight the role of localized ischemic changes, in addition to diffuse axonal injury. Values of over 8 mm for the width of the third ventricle and over 11 mm for septum caudate distance are suggestive of catastrophic and poor prognosis for recovery.

Practice of prophylactic anticonvulsant treatment in head injury

The policy of patient selection for prophylactic anticonvulsant treatment has been evaluated retrospectively in 124 head-injured patients admitted consecutively for rehabilitation after primary neurosurgical treatment. Prophylaxis had been instituted in about 60% (51/83) of high risk patients and in about 30% (12/41) of the patients who did not belong to the high risk categories. The use of existing risk data as guidelines for decisions about anticonvulsant prophylaxis is discussed.

Late neuropsychologic status after childhood head trauma

A neurologic and neuropsychologic test battery was administered to a sample of 35 children drawn from all those in a defined geographic area who had been hospitalized for head trauma before age 7 during the years 1970-1976. Examination was performed 3 1/2 to 10 years after injury, at age 6-15. Twelve subjects had been diagnosed at the time of injury as suffering moderate insult and had been referred to the metropolitan neurosurgical center, while twenty-three with only mild injury had been retained for observation in a local pediatric ward. The twelve with more severe insult were significantly inferior to the other subjects on the Block Design and Coding subtests of the revised Wechsler Intelligence Scale for Children. The Koppitz score of the Bender Test, the WISC-R scatter, the Benton Visual Retention Test, the GATB Motor Speed Test and the Bourdon-Wiersma Vigilance Test showed less diagnostic power and failed to distinguish between the group with more severe injury and that with less. A detailed and carefully scored neurologic examination also failed to distinguish between the two groups. The findings suggest that relatively common traumatic injury may be associated with detectable late cognitive deficit, and that some WISC-R subtests may be among the best measures for detecting such deficit.