A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23.

Childhood ataxias are a complex set of inherited disorders. Ataxias associated with generalized tonic-clonic epilepsy are usually included with the progressive myoclonus epilepsies (PME). Five disease entities, Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinoses, myoclonic epilepsy with ragged red fibres and sialidoses, account for the majority of PME cases. Two rare forms of ataxia plus epilepsy, sensory ataxic neuropathy, dysarthria and ophthalmoparesis, and infantile onset spinocerebellar ataxia were described recently and found to be caused by defective mitochondrial proteins. We report here a large consanguineous family from Saudi Arabia with four affected children presenting with generalized tonic-clonic epilepsy, ataxia and mental retardation, but neither myoclonus nor mental deterioration. MRI and muscle biopsy of one patient revealed, respectively, posterior white matter hyperintensities and vacuolization of the sarcotubular system. We localized the defective gene by homozygosity mapping to a 19 Mb interval in 16q21-q23 between markers D16S3091 and D16S3050. Linkage studies in this region will allow testing for homogeneity of this novel ataxia-epilepsy entity.

The use of F-wave and sural potential in the diagnosis of subclincal diabetic neuropathy in Saudi patients.

OBJECTIVE: To compare nerve conduction parameters in asymptomatic diabetic patients and with no clinical signs of neuropathy and in control subjects. METHODS: Forty-eight diabetic Saudi subjects (20 males, 28 females) and 48 age-and-sex-matched control subjects were studied. The mean age of patients +/- standard deviation was 45.6+/-11.7 years. The mean duration of diabetes from time of diagnosis was 10.8+/-3.1 years, and their mean fasting plasma glucose was 8.5+/-0.9 mmol/l. Nerve conduction studies were performed on the right lower limb. RESULTS: In diabetic patients the tibial and peroneal nerve conduction velocity values were 48.6+/-4.7 and 46.3+/-5.2 m/s. They were not significantly different from controls (p>0.01). The tibial and peroneal distal motor latency values were 5.1+/-0.6 and 4.7+/-0.9 ms, and not significantly different from controls (p>0.01). The sural nerve distal sensory latency in patients was 3.2+/-0.7 ms and the sural sensory nerve action potential amplitude was 4.9+/-2.5 uV. These values were significantly different from controls (p<0.01). The tibial and peroneal minimal F-wave latency values in patients were 32.5+/-1.9 ms/m and 32.9+/-1.6 ms/m, and were significantly different from controls (p<0.001). The F-wave average duration values in patients were 11.8+/-1.5 ms for the tibial nerve and 9.0+/-1.4 ms for the peroneal nerve. These were significantly different from control (p<0.001). CONCLUSION: The peroneal and tibial minimal F-latency and average F-duration provide the most sensitive nerve conduction; indicators for the diagnosis of subclinical neuropathy in diabetes.

Autosomal recessive hereditary neuropathy with focally folded myelin sheaths and linked to chromosome 11q23: a distinct and homogeneous entity.

We describe a six generation Saudi kindred, with a recessive hereditary motor and sensory neuropathy (HMSN). Four individuals were affected including two children (a boy and a girl) and a 23-year-old man. The fourth (a female) died at the age of 14 years. Onset of the disease was early (< 2 years) and the clinical and neurophysiological features were, generally, quite similar to those of an Italian family linked to chromosome 11q23. The peculiar pathologic pattern was irregular and redundant loops associated with folding of the myelin sheaths. The genetic study confirmed linkage to chromosome 11q23 and refined the location of the gene between D11S1311 and D11S917, a 3.3 cM region. These findings support the existence of a homogeneous and distinct entity within the form of HMSN associated with focally folded myelin sheaths.

The diaphragmatic compound muscle action potentials (DCMAPs) at different lung volumes--a prospective electrophysiological study of the respiratory system.

Phrenic nerve conduction study and measurements of static lung volumes such as functional residual capacity (FRC), total lung capacity (TLC) and residual volumes (RV) using body plethysmography were carried out in 31 normal healthy male subjects (31 +/- 8 years). The objective was to correlate changes in latency, amplitude, duration and area of diaphragmatic compound muscle action potential (DCMAPs) with lung volumes and changes in them with changes in postures. The mean phrenic nerve latency did not show any significant change with lung volumes or postures, but the latency and height of the subject had a significant correlationship (r = 0.68). The peak to peak amplitude of DCMAP showed a significant relationship with the quantitative lung volumes (r = 0.65). The amplitude was significantly higher and duration reduced (p < 0.001) at TLC as compared with those at measured FRC and RV in both sitting and supine postures. The area under the curve did not change significantly. Similarly, amplitudes and latency did not show any significant relation with other anthropometric parameters. The study evaluates a new quantitative relationship between DCMAPs amplitude and lung volumes. This may be carefully used along with other clinical parameters in critically ill patients for an early weaning from ventilator. Posture exerts minimal influence on DCMAPs amplitude; since DCMAPs amplitudes depends on the position of the diaphragm which in turn depends on dipolic potential, its electromagnetic fields and its moving angle subtends at the recording electrode, one can confidently use it to predict lung volume in respiratory failure due to neuromuscular diseases where subjective lung function assessment is impossible. However, a further study is in process in the critical care unit to confirm its utility.

Motor terminal latency index in carpal tunnel syndrome.

We determined the motor terminal latency index (MTLI) of the median nerve across the carpal tunnel in 41 upper extremities of 31 patients with carpal tunnel syndrome. Changes in motor nerve conduction velocity (MNCV), motor terminal latency (MTL), sensory action potential and the amplitude of the compound muscle action potential recorded from the abductor pollicis brevis muscle were all suggestive of proximal and distal segment involvement of the nerve across the carpal tunnel. There was no correlation between forearm MNCV and MTL (r = 0.40), although MTLI was correlated with MTL (r = 0.67) but not with MNCV, indicating a disproportionate conduction across the carpal tunnel.

Terminal Latency Index: A distinctive diagnostic criterion for carpal tunnel syndrome.

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Motor terminal latency index in carpal tunnel syndrome

We determined the motor terminal latency index [MTLI] of the median nerve across the carpal tunnel in 41 upper extremities of 31 patients with carpal tunnel syndrome. Changes in motor nerve conduction velocity [MNCV], motor terminal latency [MTL], sensory action potential and the amplitude of the compound muscle action potential recorded from the abductor pollicis brevis muscle were all suggestive of proximal and distal segment involvement of the nerve across the carpal tunnel. There was no correlation between forearm MNCV and MTL [r = 0.40], although MTLI was correlated with MTL [r = 0.67] but not with MNCV, indicating a disproportionate conduction across the carpal tunnel

Hemiconvulsion-hemiplegia-epilepsy syndrome. A clinical, electroencephalographic and neuroradiological study.

Six patients (4 boys and 2 girls) with hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome are described. They had prolonged seizures, lasting from 30 min to 12 h, at ages 1-4 years. These took the form of hemiconvulsion in three of the children and generalized tonic-clonic seizures in the others, being preceded by hemifacial twitching or head and eye deviation in two. They were followed by hemiplegia, which cleared with time in five patients, apart from subtle pyramidal tract signs. One child had spastic quadriparesis, choreiform movements, contracture deformities and severe mental retardation following repeated status epilepticus. Subsequent epilepsy developed in five patients and was satisfactorily controlled with carbamazepine and/or phenobarbitone. Cerebral hemiatrophy was documented in all patients by cranial computed tomography and/or magnetic resonance imaging. Single photon emission computed tomography (done in 4 patients) showed ipsilateral hypoperfusion (of the damaged hemisphere). Electroencephalography showed ipsilateral slowing and low voltage of background activity. Epileptiform discharges were found on the ipsilateral side in two cases and the contralateral side (the undamaged hemisphere) in one.

Centro-temporal benign epilepsy in Saudi children.

A review of 36 interictal EEGs compatible with the diagnosis of benign childhood epilepsy with centro-temporal spikes (BECTS) was made in this study. These children constituted 31% of the children with focal epileptic EEG activity observed in the same period. The dipolic spikes occurred either as a single focus (78%) or as two independent foci with a greater preponderance to the right (22%). The onset of seizures before the age of 5 years (Group I) is 53% and between 6 and 10 years (Group II) is 47%. Clinical evaluation showed that 60% of the patients in Group I and 75% in Group II had lateralized seizures, although all of them were initially diagnosed as nocturnal generalized tonic-clonic seizures. A follow-up study showed 31% complete recovery, 47% seizure-free under medications, 8% occasional seizures, 8% frequent seizures, and the rest 6% had a single seizure without medication. It is therefore concluded that the syndrome is common in Saudi Arabia and is usually unrecognized by the general physicians. The follow-up of our patients so far confirms the excellent prognosis.

Nocturnal epilepsies in adults.

We evaluated the clinical characteristics and the electroencephalographic (EEG) findings by long video-EEG monitoring in 64 successive patients with definite nocturnal seizures. Mental state, neurological examination, neuroimaging and EEG background were normal in all patients. Classification of epilepsies was possible in 42 out of 64 (66%) patients according to the revised Classification of Epilepsies and Epileptic Syndromes by the Commission on Classification and Terminology of International League Against Epilepsy (1989). Out of those 42 patients, 33 (79%) had partial epilepsies, while 9 (21%) had generalized epilepsies. Response to antiepileptic drugs was excellent and only 4 (6%) patients had one seizure attack per year, two of them were on two antiepileptic drugs while the others were free of seizure on a single drug during the 2 years of follow-up. It seems that nocturnal seizures in adults form a new distinctive partial epileptic syndrome of a benign entity.

Nonketotic hyperglycinemia: A life-threatening disorder in Saudi newborns.

Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder due to a fundamental defect in the glycine cleavage system, which leads to neuronal dysfunction caused by two receptor-mediated mechanisms. It is a life-threatening condition in the neonate. Until now, the disease has not been described from Saudi Arabia. We report on three Saudi newborns (two males and one female) who had NKH. Two of these were siblings (male and female). Following uneventful deliveries, they presented between the first and third day of life with progressive lethargy, poor feeding, recurrent apnea and severe hypotonia. Two newborns had myoclonic seizures, whereas electroencephalogram showed burst-suppression pattern in all of them. The diagnosis was confirmed by high cerebrospinal fluid/plasma glycine ratio (0.2 and 1.08) in two patients (normal < 0.030, whereas a sibling of one of the neonates had a high glycine level. Both siblings died during the second month of life despite therapy with dextromethorphan (an N-methyl-D-asparate [NMDA] receptor antagonist) in one of them. The third day had ketamine (noncompetitive NMDA receptor antagonist) and sodium benzoate (that conjugates with glycine, forming nontoxic hippuric acid). Although his seizures were controlled, he survived with severe neurological sequelae.

Diagnostic role of brain-stem auditory evoked potentials in neurobrucellosis.

Evoked potential audiometry and brain-stem auditory evoked potentials were evaluated in 15 patients with systemic brucellosis in whom brucella meningitis was suspected clinically. In 8 patients cerebrospinal fluid (CSF) was abnormal with high brucella titre, and evoked potentials were abnormal in all of them. In 7 patients the CSF was normal and evoked potentials were also normal. Brain-stem auditory evoked potential abnormalities were categorised into 4 types: (1) abnormal wave I, (2) abnormal wave V, both irreversible, (3) prolonged I-III interpeak latencies, and (4) prolonged I-V interpeak latencies, both reversible. These findings are of important diagnostic value and correlate well with the clinical features, aetiopathogenesis and final outcome.

Measurement of reversibility of airways obstruction: which parameters to use?

Maximum expiratory flow-volume (MEFV) curves recorded before and after salbutamol inhalation on 100 patients with various lung diseases were studied. Improvement was found to occur more frequently in MEF50, FEF25-75, FVC and MEF25, than in FEV1, FEV1/FVC%, or MTT. If improvement in only one of the first four parameters was taken as a measure of reversibility of airways obstruction, many cases showing improvement in the others were missed. Improvement in any of the last three parameters was rarely missed if improvement in any of the first four was present. It was concluded that there is no single best measurement for assessment of bronchodilator response. FVC, FEF25-75, MEF50 and MEF25 should all be measured. A flow-volume record of forced expiration from which all these measurements can be derived would therefore be preferable for this purpose to the time-volume spirometer record from which only FVC and FEF25-75 can be determined.

Bronchial reactivity and small airway dysfunction in subjects with intermediate alpha 1-antitrypsin deficiency.

Lesions in small airways may cause increased central deposition of inhaled aerosol. This may enhance airway constriction following methacholine (MCh) challenge. Heterozygous alpha 1-antitrypsin deficiency (PiMZ) and smoking may both act on the lung parenchyma and may also influence small airways. We, therefore, have related bronchial reactivity to MCh to the function of the small airways and to smoking habits in 31 normal (PiM) male subjects aged 48-50 years and 34 PiMZ male subjects, all from a population study. A total of 23 subjects with increased bronchial reactivity was found. The number of reacting smokers (14/23) was significantly higher than that of the reacting ex-smokers (7/23) (p less than 0.05) and nonsmokers (2/19) (p less than 0.05). The smokers who had increased reactivity to MCh challenge had significantly higher closing capacity %, RV/TLC %, and volume of trapped gas % than the smokers who did not have increased reactivity. This difference was not seen with regard to closing volume %, slope index, delta N2 %/1, or washout volume. There was no significant difference between the PiM and the PiMZ subjects with regard to any of the lung function variables or the response to the MCh challenge. It is concluded that there may be a correlation between dysfunction of the small airways and increased bronchial reactivity.

Bronchial reactivity, smoking, and alpha1-antitrypsin. A population-based study of middle-aged men.

We assessed bronchial reactivity to increasing doses of inhaled methacholine (MCH) in a population-based study on alpha1-antitrypsin. We compared 34 consecutive 48- to 50-yr-old heterozygous (Pi-MZ) men with 31 men of the same age with normal Pi phenotype (Pi-M) matched for smoking habits. There was no significant difference between control FEV1 or in MCH reactivity between the Pi-MZ and the Pi-M group. Twelve Pi-MZ subjects and 11 Pi-M subjects showed a fall of greater than or equal to 15% of FEV1 (PC 15%). Smokers showed increased sensitivity to MCH in both phenotype groups, although there was no significant difference in control FEV1 between the smoking and nonsmoking groups. Eleven smokers and ex-smokers, 5 with histories of asthma or sputum production, showed bronchial hyperreactivity, i.e., PC 15% FEV1, to 0.1% MCH or lower concentrations. Among nonsmokers there was 1 reactor and 1 hyperreactor. We conclude that heterozygous alpha1-antitrypsin deficiency (Pi-MZ) does not increase bronchial reactivity and that smoking does.

Drug-induced changes in airways obstruction reflected by forced expiratory flows and airway resistance measured with an oscillometric method using quiet breathing.

14 patients with partially reversible airways obstruction were studied with forced expiratory flows (FEV1, PEFR) and with airway resistance measured by an oscillometric method (Siregnost FD-5) before and after drug-induced changes in airways obstruction. 10 inhaled methacholine to induce bronchoconstriction, and 4 inhaled salbutamol and an additional dose of neosynephrine to induce bronchodilation. Intraindividual changes in resistance (Rosc) measured by the oscillometer with quiet breathing showed a fair significant correlation with changes in FEV1 (r = 0.54, p less than 0.05) and changes in PEFR measured by the Wright peak flow meter (r = 0.59, p less than 0.05). The present type of oscillator can be used for provocations starting from normal airway resistance but not for measures of treatment effects in markedly obstructive patients.