PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection).

PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection) is a rare condition first described in 1998. It describes the presence of obsessive-compulsive disorder (OCD) or tics with an episodic course, and a temporal relationship to Group A beta haemolytic streptococcal infection (GABHS). Recurrent episodes can be disruptive and upsetting for a child, but the best way to treat the condition has yet to be established. Penicillin prophylaxis has not proved effective, and other therapies are experimental. There is some evidence in the literature to support the role of tonsillectomy in improving the condition. We report a case of a 6-year-old boy who presented with tic and hemi-chorea associated with GABHS throat infection. He had a recurrence of his symptoms associated with a further GABHS infection, but has had no further symptoms following tonsillectomy. This case report lends further evidence to the role of tonsillectomy in the management of PANDAS.

The use of lamotrigine, vigabatrin and gabapentin as add-on therapy in intractable epilepsy of childhood.

PURPOSE: Lamotrigine (LTG), vigabatrin (VGB) and gabapentin (GBP) are three anti-epileptic drugs (AEDs) used in the treatment of children with epilepsy for which long-term retention rates are not currently well known. This study examines the efficacy, long-term survival and adverse event profile of these three agents used as add-on therapy in children with refractory epilepsy over a 10-year period. METHODS: Three separate audits were conducted between February 1996 and September 2000. All children studied had epilepsy refractory to other AEDs. Efficacy was confirmed if a patient became seizure free or achieved >50% reduction in seizure frequency for 6 months or more after starting therapy. Adverse events and patient survival for each drug were recorded at the end of the study period. RESULTS: Between September 1990 and February 1996, 132 children received LTG, 80 VGB and 39 GBP. At the 10-year follow-up audit, 33% of the children on LTG had a sustained beneficial effect on their seizure frequency in contrast to 19% for VGB and 15% for GBP. No significant difference in efficacy was found in children with partial seizures. Children with epileptic encephalopathy (EE) including myoclonic-astatic epilepsy and Lennox-Gastaut Syndrome (LGS) achieved a more favorable response to LTG. The main reasons for drug withdrawal were lack of efficacy for VGB, apparent worsening of seizures for GBP and the development of a rash for LTG. CONCLUSIONS: Lamotrigine is a useful add-on therapy in treating children with epilepsy. It has a low adverse event profile and a sustained beneficial effect in children with intractable epilepsy.

Audit of the management of convulsive status epilepticus in children: the need for a uniform treatment strategy.

We conducted a two-year prospective audit to review the paediatric management of Convulsive Status Epilepticus (CSE) in Ireland. Our audit showed that there is considerable variability in the management of CSE in this country. In order to provide optimum care for this potentially life-threatening condition a uniform management strategy is required. We propose a protocol for the treatment of CSE, which should ensure uniform management and optimum care and also provide a template for further study and audit of this important disorder.

Familial childhood onset neuropathy and cirrhosis with the 4977bp mitochondrial DNA deletion.

The common 4977 base pair mitochondrial deletion has been identified in association with a number of distinct clinical phenotypes. These include the Kearns-Sayre syndrome, the Pearson marrow-pancreas syndrome, and chronic progressive external ophthalmoplegia. We report the clinical and pathological findings in two siblings in whom the 4977 base pair mitochondrial DNA deletion was identified in muscle-derived mitochondrial DNA. One sibling manifested early onset liver and renal failure, and both developed prominent peripheral sensorimotor neuropathy. These clinical findings have not been previously described in association with the 4977bp mtDNA deletion and thus represent a further expansion of the spectrum of mitochondrial disease.

Focal upper limb neuropathy in a child.

A 9-year-old girl presented with a 4-week history of right upper limb weakness. Clinical assessment and neurophysiological studies suggested an atypical brachial plexitis. She re-presented 3 1/2 years later with progressive muscle weakness involving both legs and left arm and hand. There had been no interval improvement in her right upper limb. Clinical, neurophysiological and pathological findings were consistent with chronic inflammatory demyelinating polyneuropathy. She responded to a single course of intravenous immunoglobulin--and review more than 6 years after treatment confirms that she remains functionally normal. Focal upper limb neuropathy preceding a diffuse demyelinating process by several years has not been previously described in a child. Long-term follow-up of this patient allows us to comment on the natural history of her condition and the apparent long-term efficacy of intravenous immunoglobulin in this case.

Prognosis in Guillain-Barré syndrome.

Clinical recovery started in 23 children with Guillain-Barré syndrome after a mean time of 19 days and to full recovery in 15 was 6.2 months. Long term follow up indicated that 19 with acute onset had completely recovered clinically and three with subacute onset had a chronic relapsing or protracted course.

Fatal nemaline myopathy in infancy.

The clinical and neuropathological findings in two infants with congenital nemaline myopathy are described. One patient presented at birth with severe hypotonia, respiratory failure and contractures and died shortly after the neonatal period. The other presented at age two months with hypotonia and, following a period of clinical stability, died at age seven months from respiratory failure. Pathological findings in the fatal neonatal case revealed numerous rod bodies in lingual, pharyngeal, diaphragm and limb muscles, correlating with clinical findings. Significant, but less rod body involvement was found in the diaphragm and limb muscles of the second patient. Although a neural basis has been suggested for this disorder, no abnormalities were found in the central nervous system or in the peripheral nerves of these two severely affected patients.

Bacterial meningitis in infancy: effects on intracranial pressure and cerebral blood flow velocity.

The effects of acute bacterial meningitis on intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) were studied in four older infants (mean age, 5.75 months) and in four newborns. ICP and CBFV were affected in the older infants, but not in the newborns. In the older infants, ICP was markedly elevated in the first 2 days of illness (mean peak ICP, 240 mm H2O). With resolution of intracranial hypertension in the next few days, CBFV increased approximately 80%. In the newborns, there was no marked elevation of ICP or change in CBFV. Impaired cerebral perfusion, due to intracranial hypertension, is a potential cause of brain injury in older infants. Other mechanisms of brain injury may be more important in newborns.

Outcome of neonatal intraventricular hemorrhage with periventricular echodense lesions.

The incidence of periventricular-intraventricular hemorrhage (PV-IVH) in a group of 460 preterm infants with birth weight less than 2,250 gm, studied by cranial ultrasonography, was 39%. Sixty-four (36%) of the infants with periventricular-intraventricular hemorrhage had, in addition, periventricular intraparenchymal echodensity (IPE) evident on ultrasound scan. Thirty-three of the 64 infants had large IPE, and 31 had small IPE. Large IPE consisted of globular echodensity, most often on the side of maximum intraventricular hemorrhage, extending from the external angle of the lateral ventricle into major portions of the white matter of the frontal and parietal lobes; small IPE, often bilateral, consisted of linear echodensity extending for a few millimeters from the external angle of the lateral ventricle into the periventricular white matter. The outcome for infants with large and small IPE differed markedly. Mortality was greatest (94%) for infants with large IPE and birth weight less than 1,000 gm. All survivors with large IPE, regardless of birth weight, had moderate to severe neurological deficits evident on follow-up. In contrast, infants with small IPE and birth weight less than 1,000 gm had a mortality of 38%. Moreover, 70% of all survivors with small IPE were free of neurological deficits on follow-up. The difference in outcome appeared to relate in largest part to the severity of the parenchymal involvement. These data have major significance for decisions concerning management of infants with periventricular-intraventricular hemorrhage and intraparenchymal involvement.

Doppler ultrasonography in the determination of neonatal brain death.

Both clinical and electroencephalographic criteria for brain death have limited value in the newborn. A simple test to determine the cessation of cerebral blood flow would be a useful adjunct to the determination of brain death in this population. In contrast to the invasive techniques used in older patients to estimate cerebral blood flow, the Doppler technique to estimate cerebral blood flow velocity from the anterior fontanelle of the newborn is noninvasive and can be used at bedside. In this study we define the changes in the flow velocity pattern in the anterior cerebral and the common carotid arteries in six newborn infants with clinical criteria for brain death: coma, absent brainstem function, and dependence on mechanical ventilation. A characteristic sequence of deterioration of the flow velocity waveform in both vessels was defined. This sequence consisted of (1) loss of diastolic flow, (2) appearance of retrograde flow during diastole, (3) diminution in systolic flow in the anterior cerebral artery, and, ultimately, (4) no detectable flow in the anterior cerebral artery, despite considerable flow in the common carotid artery. This constellation of findings suggests a progressive increase in cerebrovascular resistance and a progressive decrease in cerebral perfusion, compatible with the diffuse cerebral necrosis and edema documented postmortem. We conclude that the transcutaneous Doppler technique is a useful complement to other noninvasive methods, especially clinical assessment, in the determination of brain death in the newborn.

Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome. Relation to the development of intraventricular hemorrhage.

We studied whether changes in cerebral blood-flow velocity occur during the respiratory-distress syndrome and whether, if present, they are related to the subsequent occurrence of intraventricular hemorrhage. Fifty infants weighing less than 1500 g at birth who required mechanical ventilation for the respiratory-distress syndrome were studied from the first hours of life. Blood-flow velocity in the anterior cerebral artery was measured at the anterior fontanel by means of the Doppler technique. At 12 hours of age, the infants had blood-flow velocity patterns that were either stable or fluctuating and that reflected the patterns of simultaneously recorded blood pressure. Intraventricular hemorrhage subsequently developed in 21 of 23 infants with the fluctuating pattern (in most of them, within the next 24 hours), but in only 7 of 27 infants with the stable pattern. Preliminary data suggest that the cerebral hemodynamic fluctuations are related to the respiratory disease and particularly to the mechanics of respiration. We conclude that the fluctuating pattern of cerebral blood-flow velocity in infants with the respiratory-distress syndrome indicates an extreme risk of the development of intraventricular hemorrhage and may represent a major and potentially preventable etiologic factor.

Electrophysiological investigation of the auditory system in Friedreich's ataxia.

Auditory brainstem responses (ABRs) and cortical auditory evoked responses (AERs) were studied in a series of 16 Friedreich's ataxia patients who varied in age, degree of clinical involvement and duration of the disorder. The ABRs were markedly abnormal in all but the youngest patient, and the abnormalities reflected the severity and duration of the disease. The latencies of the AERs were significantly longer in the Friedreich's ataxia patients compared to normal controls, suggesting cortical as well as peripheral involvement of the auditory system. These data are discussed in terms of the neuropathology of the disorder and the similarities with the other sensory systems in Friedreich's ataxia patients.