Osteoporosis in Rett syndrome: a case study presenting a novel management intervention for severe osteoporosis.

The present article describes a successful novel therapeutic intervention with Aredia with one child with Rett syndrome, after suffering from six pathological fractures within less than 3 years due to severe osteoporosis. Since the initiation of the treatment (3 years ago), the child has not suffered any fractures. Patients with chronic diseases and those with disabilities or on anticonvulsant medications are at risk for low bone density and possibly for the resultant pathologic fractures that define osteoporosis in children. Individuals with Rett syndrome (RS) have been shown to have low bone mineral density (or osteopenia) at a young age. If osteoporosis occurs in a girl with RS, it can inflict pain and seriously impair the child's mobility and quality of life. The present article describes a case study of a child with RS (showing an average of 1.75 fractures annually for the 4 years preceding the treatment) before and after a treatment with Aredia. Patient received 30 mg/day for 3 days on a once every 3-month cycle. There was a 45 % improvement in bone mass density (BMD) values from pre-post-intervention. The child had no fractures in the 3 years posttreatment. This finding is significant (p < 0.03). The BMD Z-scores of the child showed severe osteoporosis (Z-score of -3.8) at pre-intervention and are elevated to osteopenia levels (Z-score of -1.3) at post-intervention measurements. All measurements suggest that the treatment successfully reversed the osteoporotic process and prevented further fractures. This change caused great relief to the child and her family and an improvement in their quality of life. The findings support the ability (in one case) to reverse the progression of osteoporosis in individuals with Rett syndrome showing severe osteoporosis with multiple fractures.

A tale of two cities - the effect of low intensity conflict on prevalence and characteristics of musculoskeletal pain and somatic symptoms associated with chronic stress.

UNLABELLED: Although both acute and chronic stress leads to pain, the precise characteristics of this association have not been well defined. Sderot is an Israeli town exposed to repeated missile attacks. Ofakim, a town of similar demographic and socioeconomic characteristics, had not been targeted, as of the period of our study. We examined the occurrence and characteristics of pain and related somatic symptoms in Sderot and Ofakim. METHODS: One thousand and twenty-four individuals in Sderot and 1006 in Ofakim were interviewed regarding pain, somatic symptoms, mood, trauma-exposure, and general health status. RESULTS: Significantly higher levels of trauma-related symptoms and somatic symptoms were noted in Sderot compared with Ofakim (p<0.001). Chronic widespread pain (CWP) was more common in Sderot (11.1%) than Ofakim (8.3%; OR 1.37, p=0.038). Women were more likely (13.9% vs. 9.3%; OR 1.45, p=0.06) than men (8.9% vs. 7.3%, OR 1.24, p=0.37) to experience CWP in Sderot vs. Ofakim. Amongst males, chronic regional pain (CRP) was more common in Sderot (19.2%) than in Ofakim (14.2%; p=0.036). Pain severity in Sderot was significantly higher than in Ofakim (p<0.001). CONCLUSIONS: Similar to previous studies that have suggested that chronic stress is associated with chronic pain, this study demonstrates significantly increased rates of somatic complaints, including pain, fatigue and IBS-like symptoms, among individuals in Sderot compared with Ofakim, as well as significantly higher rates of trauma-related symptoms. Thus, a fibromyalgia-like symptoms cluster was more likely to be found in Sderot compared with Ofakim. Widespread pain was reported as being significantly more frequent by inhabitants of Sderot compared with Ofakim. These results have relevance to both the general population and for populations enduring chronic stress.

Sex differentials in predictors of mortality for patients with adult-onset diabetes: a population-based follow-up study in Beer-Sheva, Israel.

OBJECTIVE: To test the hypothesis that factors predicting mortality differ between diabetic men and women. RESEARCH DESIGN AND METHODS: A total of 498 known patients with diabetes residing in a well-defined geographical area and receiving primary health care in 3 primary care community clinics were interviewed and examined between 1988 and 1990. RESULTS: By 31 July 1998, after a mean follow-up period of 7.8 years, 148 patients (68 men and 80 women) had died (29.7%). No statistical differences in survival rate or in the specific causes of death were found between men and women. In the univariate analysis of factors examined at baseline, GHb levels were significantly higher among women who died compared with women who survived, but this was not the case for men. Conversely, a trend of higher triglyceride and uric acid levels was found for men who died compared with men who survived, but this was not the case for women. Multivariate Poisson regression analysis showed significantly higher risk ratios for mortality in men > or = 63 years of age, men with microalbumin excretion > or = 30 mg/l, and men with higher triglyceride levels. In contrast, the analysis in women showed that higher GHb and creatinine levels and a reported history of heart disease were the only factors at the baseline examination significantly and independently associated with an increased risk ratio of mortality. CONCLUSIONS: The results suggest the existence of sex-specific interactions with various metabolic factors associated with diabetes that may have a different effect on mortality for each sex.

Complex partial status epilepticus.

Two children had complex partial status epilepticus, a rare convulsive disorder. The presumptive clinical diagnosis was based on the complex symptomatology occurring within a fluctuating state of consciousness, and on unsustained responses. The diagnosis was confirmed by the ictal EEG, which demonstrated continuous focal discharge in the left temporal region in one patient, and by constant focal spike-and-wave activity over the right temporal areas, which occasionally became hypersynchronous, in the other. We also discuss the possible anatomical substrate and neurophysiological mechanisms of this entity.

Sleep patterns in the Lennox-Gastaut syndrome.

Serial polysomnograms were performed on 11 children with primary Lennox-Gastaut syndrome (LGS), 6 control children with other seizure disorders, and 12 who were developmentally normal. Five LGS children had abnormal polysomnograms with either complete absence or marked reduction of REM sleep; the other six LGS children had only a mild reduction of REM sleep. The percentage of REM in LGS children was less than in the controls with other seizure disorders (p less than 0.05) or the normal children (p less than 0.005). The scatter of REM percentages in LGS may imply heterogeneity of the syndrome, perhaps related to the severity of brainstem dysfunction or neurochemical derangement.

Glutaric aciduria type I: clinical heterogeneity and neuroradiologic features.

We present four patients, two pairs of siblings, with glutaric aciduria type I (GA I). All four had undetectable glutaryl-CoA dehydrogenase activity on fibroblast culture and massive urinary excretion of glutaric acid. All had serum carnitine deficiency at time of diagnosis except one patient who was diagnosed neonatally. All had a unique pattern of frontotemporal atrophy on CT. Remarkably, in both sibling pairs, one child was asymptomatic. This suggests that the biochemical markers hitherto identified with GA I do not encompass the entire scope of the metabolic or enzymatic abnormalities. Alternatively, as yet unidentified mechanisms might spare or delay the destructive process.

Striatal degeneration and spongy myelinopathy in glutaric acidemia.

The neuropathological findings in a 6 1/2-year-old boy with glutaric acidemia (GA) are described, and the pathology of 7 additional literature cases is briefly reviewed. Bilateral striatal degeneration and spongy change of the white matter were the salient features in this case and seem to represent the cardinal pathological features of the disease. Spongy myelinopathy was the result of intramyelinic vacuolation due to splitting of the myelin sheath along the intraperiod line, as illustrated here for the first time in GA. Based on morphological, biochemical and pharmacological data from humans and experimental animals, it is hypothesized that excitotoxin-mediated neuronal damage may account for the striatal degeneration, while toxic effect on myelin metabolism by the metabolic derangement of GA may explain the widespread white matter changes.

Erythrocyte (Ca2+ + Mg2+)-ATPase activity and calcium homeostasis in Duchenne muscular dystrophy.

Because the erythrocyte (RBC) in Duchenne's muscular dystrophy (DMD) is thought to be a suitable experimental paradigm for the sarcolemma, the RBC membrane-bound enzyme (Ca2+ + Mg2+)-ATPase has been investigated as to its relevance to abnormalities of calcium metabolism in DMD muscle. In this study, RBC (Ca2+ + Mg2+)-ATPase activity, intracellular calcium and potassium contents and complete hemogram were examined in 10 DMD patients and 16 age-matched controls. (Ca2+ + Mg2+)-ATPase activity was found elevated in the DMD RBC, consistent with reports from previous studies, but no abnormalities in intracellular calcium, potassium or hemograms were detected. It seems that although the (Ca2+ + Mg2+)-ATPase activity is changed, it bears no relevance to calcium homeostasis in DMD RBC. It is inferred that the increase in intramuscular calcium in DMD muscle, which is also found in other neuromuscular diseases, may be a non-specific finding in the diseased muscle and part of the final common pathway leading toward cellular degeneration and death.

Developmental dyscalculia.

We conducted a neurobehavioral evaluation on eleven children with developmental dyscalculia in order to determine which aspects of arithmetic processes are affected in this disorder. Our results indicate that memorization of numerical facts in these children was poor or virtually non-existent and the ability to solve simple arithmetic exercises impaired. By contrast, comprehension and production of number functions were intact. Although all children had been referred for evaluation of selective deficits in arithmetic skills, they also displayed a mild degree of dyslexia, dysgraphia, anomia, and grapho-motor dysfunction. We conclude that cognitive mechanisms underlying arithmetic ability can be dissociated developmentally and suggest that remediation programs be designed only after detailed analyses of arithmetic and associated cognitive skills.

Developmental dyscalculia and brain laterality.

The correlation between arithmetic dysfunction and brain laterality was studied in 25 children with developmental dyscalculia (DD). The children were tested on a standardized arithmetic battery and underwent a neurological and neuro-psychological evaluation. A diagnosis of left hemisphere dysfunction (n = 13) was based on right side soft neurological signs, performance IQ (PIQ) > verbal IQ (VIQ), dyslexia and intact visuo-spatial functions. The criteria for right hemisphere dysfunction (n = 12) were left body signs, VIQ > PIQ, impaired visuo-spatial functions and normal language skills. The groups were similar for age, gender, and socio-economic status. Our results showed that both groups scored more than 2 SD below the mean adjusted score on the arithmetic battery, but the left group was significantly worse in 3 areas: mastery of addition/subtraction, complex multiplication and division and visuo-spatial errors (p < 0.05). The data indicate that dysfunction of either hemisphere hampers arithmetic acquisition, but arithmetic impairment is more profound with left hemisphere dysfunction.

Arithmetic skills in kindergarten children with developmental language disorders.

Although arithmetic is not a language-based skill, a specific learning disability in arithmetic--dyscalculia--is commonly seen in children with developmental language disorders (DLD). The object of this study was to assess whether kindergarten children with DLD have impaired arithmetic skills and, if so, to correlate the pattern of dysfunction with language syndromes. Forty-two children with DLD attending mainstream kindergartens, and their matched controls, underwent an arithmetic battery, neurological examination, intelligence quotient (IQ) test (WPPSI/WISC-R) and language assessment (CELF-R).* Attention deficit hyperactivity disorder (ADHD) was diagnosed by psychological assessment and behaviour questionnaires. Results showed that children with DLD were similar to controls on performance IQ (104.2+/-12.1 and 109.4+/-12.7 respectively, p = NS), but inferior on both the CELF-R expressive (74.8+/-9.3 vs 95.2+/-15.1, p < 0.01) and receptive (77.5+/-10.0 vs 87.8+/-12.3, p < 0.01) language scores. Their performance on the arithmetic battery was also significantly poorer: 61.2+/-17.7 vs 77.4+/-13.7, p < 0.01. Low scores in reasoning principles and arithmetic operations were associated with both receptive and expressive language impairment, while poor performance on counting principles was primarily associated with expressive deficits. Mild motor signs and ADHD were more frequent in children with DLD (p < 0.01 and < 0.05, respectively). We concluded that the arithmetic impairment in children with DLD is pervasive, affecting a broad spectrum of skills. Whereas impairment of most arithmetic skills is associated with global language disturbances, counting correlates primarily with expressive language deficits. Anticipatory guidance by physicians will better prepare parents and educators for the multiple challenges facing children with DLD.

Cognition, attention, and behavior in Prader-Willi syndrome.

We studied the academic, cognitive, and behavior profile of 18 patients with Prader-Willi syndrome. All had severe learning disabilities in arithmetic and writing, and the majority were also dyslexic. Their average Full-Scale IQ was 73.7 +/- 8.9, which was 1 SD below normal range, whereas their performance on executive, memory, and visuospatial tasks ranged from 2.1 to 7.0 SD below the expected means. Behavioral problems were measured using the Child Behavior Checklist, on which the majority scored in the pathologic range for social and attention problems, delinquent and aggressive behavior, somatic complaints, and thought problems. Genotypes of the children did not predict cognitive or behavioral profile, nor could behavior be associated with parameters of weight or IQ. In summary, we found that patients with Prader-Willi syndrome have profound learning disabilities and cognitive deficits, greater than expected for their IQ. Behavioral problems, including attention-deficit hyperactivity disorder (ADHD), are also prevalent and impede the overall management of this group of patients. The genotypes were not helpful in predicting cognitive or behavioral patterns.

Attention-deficit hyperactivity disorder and developmental right-hemisphere syndrome: congruence and incongruence of cognitive and behavioral aspects of attention.

We studied clinical aspects of attention in three groups: children with developmental right-hemisphere syndrome and attention-deficit hyperactivity disorder (ADHD), children with ADHD only, and normal controls. The three groups (N = 54) were case-matched for age, sex, IQ, hand dominance, and socioeconomic status. ADHD was diagnosed clinically using the Diagnostic and Statistical Manual of Mental Disorders-III-Revised criteria and the Conners' Abbreviated Teacher Questionnaire. Additional aspects of attention and behavior were measured by the Child Behavior Checklist, a low-cognitive-load continuous performance task, and the visual target cancellation test (paper and pencil). Although the Child Behavior Checklist profile of attentional deficits in the two clinical groups was similar, we found that the developmental right-hemisphere syndrome group was more severely impaired on parameters of attention measured by the continuous performance task and visual target cancellation test than the children with ADHD. We conclude that the profile of attentional deficits in developmental right-hemisphere syndrome is different than that seen in children with ADHD only, possibly reflecting disparate neurologic underpinnings for the two syndromes.

Vacuolating megalencephalic leukoencephalopathy in 12 Israeli patients.

Leukodystrophy with macrocephaly as the main features of infantile neurodegenerative disease are characteristics of Canavan's disease, L-2-hydroxyglutaric aciduria, type I glutaric aciduria, and Alexander's disease. Also occasionally described are occidental congenital muscular dystrophy, G(M)2-gangliosidosis, metachromatic leukodystrophy, Krabbe's disease, and mucopolysaccharidosis. Since 1995, over 60 patients with a new syndrome, vacuolating megalencephalic leukoencephalopathy, have been described. The syndrome is characterized by macrocephaly, a slowly progressive clinical course of ataxia, spastic paraparesis, and seizure disorder with relatively spared cognition. Unlike other leukodystrophies with macrocephaly (except Alexander's disease), no metabolic marker has been found. We describe a similar group of 12 patients from two different Jewish ethnic origins in whom consanguinity is prominent. These patients have neuroimaging features and magnetic resonance spectroscopy findings indicating that there is an initial increase in white-matter edema with subsequent cystic formation. Consistent with loss of tissue in these areas, brain metabolites are reduced. The familial incidence in this group of patients is suggestive of autosomal-recessive inheritance.

Valproic acid in neonatal status convulsivus.

Valproic acid infused rectally was successful in controlling seizures in two neonates who failed to respond to conventional anti-convulsive therapy. We suggest that this drug may be a useful adjuvant in difficult cases of status convulsivus in neonates.

Developmental dyscalculia.

Developmental dyscalculia is a specific learning disability affecting the acquisition of arithmetic skills in an otherwise-normal child. Although poor teaching, environmental deprivation, and low intelligence have been implicated in the etiology of developmental dyscalculia, current data indicate that this learning disability is a brain-based disorder with a familial-genetic predisposition. The neurologic substrate of developmental dyscalculia is thought to involve both hemispheres, particularly the left parietotemporal areas. Developmental dyscalculia is a common cognitive handicap; its prevalence in the school population is about 5-6%, a frequency similar to those of developmental dyslexia and attention-deficit-hyperactivity disorder. Unlike these, however, it is as common in females as in males. Developmental dyscalculia frequently is encountered in neurologic disorders, examples of which include attention-deficit-hyperactivity disorder, developmental language disorder, epilepsy, and fragile X syndrome. The long-term prognosis of developmental dyscalculia is unknown; it appears, however, to persist, at least for the short-term, in about half of affected preteen children. The consequences of developmental dyscalculia and its impact on education, employment, and psychologic well-being of affected individuals are unknown.

Attention deficit disorder: association with familial-genetic factors.

The etiology of attention deficit disorder and hyperactivity (ADDH) is controversial because both biologic and social factors have been postulated. To study such factors, we undertook a referral study based on an entire cohort (N = 6,950) of children born in Jerusalem in 1976. Of 479 children referred for learning disabilities, hyperactivity, and behavioral problems, 381 were available for study. Information regarding obstetric, developmental, and family histories was obtained by a detailed, structured interview. A DSM-III-based questionnaire for ADDH was completed by parents and teachers. Each child underwent neurologic examination and 133 had IQ testing. Of these children, 145 fulfilled the criteria for ADDH. Our results revealed a number of significant familial-genetic factors: boys outnumbered girls by 3:1, 30% of ADDH children had siblings with learning disabilities (P less than .001); and ADDH children clustered within families of North African descent (P less than .001). The only significant developmental factor was delayed language development. Of numerous pre- and peri-natal factors investigated, only intrauterine growth retardation was significantly associated with ADDH. No correlation was found between ADDH and IQ, parental age, years of education, profession, and language spoken at home. Our study supports the hypothesis that familial-genetic factors are contributory to ADDH.

Development of color association in normal and neurologically impaired children.

Color association, defined as the ability to identify the characteristic color of familiar objects, was studied in 2 groups of brain-damaged children with language or nonlanguage impairment and in a group of control patients. The performance of the 16 control children, 3.5-4.5 years of age, was compared with that of 31 patients, 4.5-5.5 years of age; their scores were 52.4 +/- 31.3 (mean +/- SD) and 85.9 +/- 13.1, respectively (p less than 0.005). Seventeen dysphasic, brain-damaged children and 11 age-matched children with neurologic deficits but without language delay were examined. Their scores were 57.7 +/- 11.7 and 70.6 +/- 21.9, respectively (p less than 0.05). Finally, each of the brain-damaged groups was compared with age-matched controls. Although the control children performed far better than the dysphasic children (77.6 +/- 20.9 and 57.5 +/- 11.7, respectively, p less than 0.001), there was no significant difference between controls and neurologically impaired children without language delay (77.6 +/- 20.9 and 70.6 +/- 21.9, respectively). We conclude that color association in normal children is already operative at 3.5 years and approaches maturity by 4.5-5.5 years. This function was preserved in neurologically impaired children without language delay but was significantly distrubed in the dysphasic children; therefore, the use of color should be assessed in the habilitation of children.

An independent comparison of terbinafine and itraconazole in the treatment of toenail onychomycosis.

BACKGROUND: Previously, sponsored publications have shown that either terbinafine or itraconazole (pulse regimen) are effective for patients with toenail onychomycosis. However, independent comparative studies are lacking. OBJECTIVES: To objectively compare treatment with terbinafine and itraconazole in patients with toenail onychomycosis. METHODS: The effectiveness of terbinafine (250 mg/day 3 months) versus itraconazole pulse regimen (400 mg/day for the first week of each month, for three cycles) was retrospectively evaluated in patients with toenail onychomycosis using mycological tests and subjective outcome measures. Statistical analyses were performed using one-way analyses of variance (ANOVA) for continuous variables and Fisher exact tests for categorical variables. RESULTS: Included in the study were 117 patients (74 patients treated by terbinafine and 43 patients treated with itraconazole). Patients were examined at an average period of 20 months after the end of therapy. Mycological cure was observed in 70.6% and 62.8% of the patients who were treated by terbinafine or itraconazole, respectively (not statistically significant). Mean visual analogue scale assessment of treatment outcome was 79.9 mm (SD 24.7 mm) and 65.2 mm (SD 34.6 mm) for patients treated by terbinafine or itraconazole, respectively (p=0.008). When the results were stratified according to age and gender, it was observed that the advantage of terbinafine versus itraconazole retained statistical significance only for patients who were 55 years old and above, or females. CONCLUSIONS: Mycological cure proportions were not statistically significant between patients treated by terbinafine or itraconazole for toenail onychomycosis. However, better subjective outcome measures indicated an advantage for terbinafine over itraconazole, noticeable in females and patients 55 years old and above.

Gowers' sign in discitis in childhood.

Three cases of discitis in early childhood presented with acute refusal to walk or change in gait pattern without neurologic deficits. In all three, a Gowers' sign was observed, although none had muscular weakness. The diagnosis of discitis was confirmed by the characteristic radiographic findings on survey lumbosacral films and/or by a hot spot at the L3 level on technetium bone scan.