A clinical diagnostic algorithm for early onset cerebellar ataxia.

Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS) presents a diagnostic algorithm for EOAc patients. In seven consecutive steps, the algorithm leads the clinician through the diagnostic process, including EOA identification, application of the Inventory of Non-Ataxic Signs (INAS), consideration of the family history, neuro-imaging, laboratory investigations, genetic testing by array CGH and Next Generation Sequencing (NGS). In children with EOAc, this algorithm is intended to contribute to the diagnostic process and to allow uniform data entry in EOAc databases.

Pediatric stroke related to Lyme neuroborreliosis: Data from the Swiss NeuroPaediatric Stroke Registry and literature review.

BACKGROUND: Cerebrovascular complications of Lyme neuroborreliosis (LNB) are poorly documented in the paediatric population. METHODS: We performed a retrospective analysis from prospectively registered cases of acute ischemic stroke (AIS) from the Swiss NeuroPaediatric Stroke Registry (SNPSR) from 2000 to 2015. Only cases with serologically confirmed LNB were included. In addition, a literature review on paediatric stroke cases secondary to Lyme neuroborreliosis in the same time frame was performed. RESULTS: 4 children out of 229 children with arterial ischemic childhood stroke and serologically confirmed LNB were identified in the SNPSR giving a global incidence of 1.7%. Median age was 9.9 years. A prior history of tick bites or erythema migrans (EM) was reported in two cases. Clinical presenting signs were suggestive of acute cerebellar/brainstem dysfunction. On imaging, three children demonstrated a stroke in the distribution of the posterior inferior cerebellar artery. The remaining fourth child had a "stroke-like" picture with scattered white matter lesions and a multifocal vasculitis with prominent basilar artery involvement. Lymphocytic pleocytosis as well as intrathecal synthesis of Borrelia burgdorferi antibodies were typical biological features. Acute intravenous third generation cephalosporins proved to be effective with rapid improvement in all patients. No child had recurrent stroke. Data from the literature concerning eight patients gave similar results, with prominent posterior circulation stroke, multifocal vasculitis and abnormal CSF as distinctive features. CONCLUSIONS: Lyme Neuroborreliosis accounts for a small proportion of paediatric stroke even in an endemic country. The strong predilection towards posterior cerebral circulation with clinical occurrence of brainstem signs associated with meningeal symptoms and CSF lymphocytosis are suggestive features that should rapidly point to the diagnosis. This can be confirmed by appropriate serological testing in the serum and CSF. Clinicians must be aware of this rare neurological complication of Lyme disease that demands specific antibiotic treatment.

[Childhood stroke : What are the special features of childhood stroke?] / "Childhood stroke" : Was macht den Schlaganfall beim Kind besonders?

Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child's individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.

Visuospatial working memory in very preterm and term born children--impact of age and performance.

Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7-12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.

[Arterial-ischaemic stroke in childhood]. / Der arteriell-ischämische Schlaganfall im Kindesalter.

The risk to have a stroke during childhood is at least as frequent as to suffer from a brain tumour. Unlike adults, in whom ischaemic strokes overweigh haemorrhagic strokes, ischaemic and haemorrhagic strokes are equally frequent in children, occurring with an incidence of 2 - 3/100'000 children/year. Even though the clinical presentation of arterial-ischaemic stroke in children (pedAIS) is similar to adults, time to diagnosis is longer. The delay to diagnosis is mainly explained by the low index of suspicion of both the general population and the medical personnel, a broad range of differential diagnoses, and the fact that diagnostic imaging in children often requires sedation, which is not always readily available. PedAIS is a multiple risk problem, usually occurring due to a combination of risk factors, such as infectious diseases, dehydration, trauma or an underlying condition such as congenital heart disease. Still little is known about the appropriate management of pedAIS. Supportive measures are considered to be the mainstay of therapy. The use of antithrombotic medication depends on pedAIS aetiology. In an ongoing multicenter trial, the safety and effectiveness of thrombolysis are currently being investigated. PedAIS carries an important mortality and morbidity, with neurological and neuropsychological deficits persisting in two thirds of the affected children.

[Traumatic brain injury in children]. / Das Schädelhirntrauma im Kindesalter.

The general practitioner has an important role in the acute management and during the rehabilitation process of children after a traumatic head injury. Latest research shows that sequelae may occur even after a mild head injury without loss of consciousness. Recognizing the warning signs and symptoms after a head injury allows the general practitioner to counsel the child and parents in secondary prevention, particularly in order to avoid any further head injury during the recovery phase. Under the supervision of the general practitioner, a gradual progressive return to the child's everyday activities optimizes the chances of a rapid and complete recovery.

Contiguous ∼16 Mb 1p36 deletion: Dominant features of classical distal 1p36 monosomy with haplo-lethality.

Monosomy 1p36 results from heterozygous deletions of the terminal short chromosome 1 arm, the most common terminal deletion in humans. The microdeletion is split in two usually non-overlapping and clinically distinct classical distal and proximal 1p36 monosomy syndromes. Using comparative genome hybridization, MLPA and qPCR we identified the largest contiguous ∼16 Mb terminal 1p36 deletion reported to date. It covers both distal and proximal regions, causes a neonatally lethal variant with virtually exclusive features of distal 1p36 monosomy, highlighting the key importance of the gene-rich distal region for the "compound" 1p36 phenotype and a threshold deletion-size effect for haplo-lethality.

Cavernous malformations of the central nervous system in children: presentation, treatment and outcome of 20 cases.

BACKGROUND: Cavernous malformations (CM) of the central nervous system are vascular malformations responsible for symptoms such as seizures, headache, and neurological deficits: 25% of cases already present in childhood. MATERIAL AND METHODS: Retrospective study including all CMs of the central nervous system in childhood diagnosed in the period 1993-2008 in 3 paediatric hospitals in Switzerland, focusing on clinical manifestations, neuroimaging findings, treatment, and outcome. RESULTS: 20 children (13 females) were diagnosed with CM, with an average age at presentation of 8.5 years (range 7 months-16 years). 17/20 presented with acute haemorrhage, 9/17 with seizures, 5/17 with focal neurological symptoms, and 3/17 with severe headache only. Localisation was supratentorial in 15/20, infratentorial in 2/20, supra- and infratentorial in 2/20, and spinal in 1 child. Five children had multiple CMs. Treatment was conservative in 10 cases and surgery was indicated in 10: for acute haemorrhage in 5; recurrent bleeding in 3; and epilepsy in 2. Follow-up after diagnosis was 0.5 years-10 years (mean 4 years), revealing neurological sequelae in 6 patients. The CM increased in size in 2 cases with an increase in number also in 1 of these. CONCLUSIONS: We confirm that CMs in childhood mainly present with seizures, severe headache, or focal symptoms due to acute haemorrhage. During infancy they may appear as dynamic lesions increasing in size and/or number. The regular application of newer neuroimaging techniques such as susceptibility weighted imaging will detect more lesions but not necessarily resolve problems concerning optimum treatment.

Acute transverse myelitis in Lyme neuroborreliosis.

INTRODUCTION: Acute transverse myelitis (ATM) is a rare disorder (1-8 new cases per million of population per year), with 20% of all cases occurring in patients younger than 18 years of age. Diagnosis requires clinical symptoms and evidence of inflammation within the spinal cord (cerebrospinal fluid and/or magnetic resonance imaging). ATM due to neuroborreliosis typically presents with impressive clinical manifestations. CASE PRESENTATION: Here we present a case of Lyme neuroborreliosis-associated ATM with severe MRI and CSF findings, but surprisingly few clinical manifestations and late conversion of the immunoglobulin G CSF/blood index of Borrelia burgdorferi sensu lato. CONCLUSION: Clinical symptoms and signs of neuroborrelial ATM may be minimal, even in cases with severe involvement of the spine, as shown by imaging studies. The CSF/blood index can be negative in the early stages and does not exclude Lyme neuroborreliosis; if there is strong clinical suspicion of Lyme neuroborreliosis, appropriate treatment should be started and the CSF/blood index repeated to confirm the diagnosis.

Cerebellar cleft: a form of prenatal cerebellar disruption.

In contrast to malformations, cerebellar disruptions have attracted little interest in the literature. We draw attention for the first time to the hypothesis that cerebellar clefts are residual changes following a prenatal cerebellar insult, and represent disruptions. We reviewed the clinical records and MR findings of six patients with a cerebellar cleft, two of whom also had prenatal MRI at 24 weeks of gestation. The clefts were located in the left cerebellar hemisphere in five cases, in the right in one patient. Other typical findings included disorderly alignment of the cerebellar folia and fissures, irregular gray/white matter junction, and abnormal arborization of the white matter in all patients. The cerebellar cleft extended into the fourth ventricle in three cases, and in two children cystic cortical lesions were seen. Supratentorial schizencephaly was found in two patients. In two patients there was a documented fetal cerebellar hemorrhage at 24 weeks of gestation. We conclude that cerebellar clefts are residual changes resulting from a prenatal cerebellar insult and consequently represent disruptions rather than primary malformations. The supratentorial findings are also in agreement with an acquired lesion. The outcome in these children was variable, mainly depending of the presence of supratentorial lesions.

[Vasculitis as a reason of chronic headache]. / Vaskulitis als Ursache von Kopfschmerzen. Systemischer Lupus erythematodes.

A 13-year-old girl presented to our emergency with a one week history of fever and skin rash and new onset of chorea for the last three days. There was a long standing history of right predominant headache; followed by personality change, fatigue, arthralgia and weight loss over the last few months. Previous investigations by head CT and ophthalmological examination did not explain the symptoms. Further investigations revealed peri- and pancarditis with aortic insufficiency, a renal involvement with elevated creatinin, protein- and hematuria and a hemolytic anemia. Diagnosis of lupus eythematodes was confirmed by high ANA, anti-dsDNS and Anticardiolipin antibodies. Within the first 48 hours after admission there was significant deterioration with reduced vigilance and dysarthria. MRI of the brain and dopplersonography of cerebral vessels showed a complete thrombosis of the right medial cerebral artery with a small net of collaterals, irregularities of the left cerebral artery due to vasculitis and several subacute leftsided ischemias. Immunosuppressive therapy with high-dose corticosteroids and cyclophosphamid together with antithrombotic therapy induced an improvement of neurologic, renal and cardiac function.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial.

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

Neuropsychological problems after paediatric stroke: two year follow-up of Swiss children.

AIM: The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. METHODS: Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. RESULTS: 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. CONCLUSION: After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.

[Neuropediatric emergencies--epileptic seizures and acute hemiplegia]. / Neuropädiatrische Notfälle--der epileptische Anfall und die akute Hemiparese.

Status epilepticus and stroke are life-threatening neurological emergencies and immediate recognition and medical management are imperativ. There is a serious risk of neurological sequelae. To limit secondary brain damage a prolonged seizure has to be treated without delay. After a short history and clinical evaluation (principles of resuscitation) a benzodiazepine (usually diazepam or lorazepam) has to be administered and in case of persistence of seizure-activity phenytoin or phenobarbital. Blood- and urine-sample must be collected in the acute phase to perform further metabolic or toxic examinations. A paralysis with acute onset is suspicious for ischaemic or haemorrhagic stroke. A precise neurological examination is mandatory for accurate neuroradiological work-up and to initiate appropriate investigations for risk factors. These patients require an immediate interdisciplinary treatment in a tertiary care centre with neuropaediatry, neuroradiology and neurosurgery.

The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors.

We report the results of three years of the population-based, prospective Swiss NeuroPaediatric Stroke Registry (SNPSR) of children (up to 16 years) with childhood arterial ischaemic stroke (AIS1), neonatal stroke (AIS2), or symptomatic sinus venous thrombosis (SVT). Data on risk factors (RF), presentation, diagnostic work-up, localisation, and short-term neurological outcome were collected. 80 children (54 males) have been included, 40 AIS1, 23 AIS2, and 17 SVT. The data presented will be concentrated on AIS. The presentation for AIS1 was hemiparesis in 77% and cerebellar symptoms and seizures in 20%, respectively. AIS2 presented in 83% with seizures and in 38% with abnormality of muscle tone. Two or more RF were detected in 54%, one RF in 35%. The most prominent RF for AIS1 were infections (40%), followed by cardiopathies and coagulopathies (25% each). AIS2 were frequently related to birth problems. Neurological outcomes in AIS1 and AIS2 were moderate/severe in 45 % and 32 %, respectively. The outcome correlated significantly with the size of infarction (p = 0.013) and age at stroke (p = 0.027). The overall mortality was 6%. Paediatric stroke is a multiple risk problem, which leads to important long-term sequelae.

[Suspected muscular disease: what to do?]. / Verdacht auf Muskelerkrankung: was nun?

During the last decades important progress in knowledge of hereditary neuromuscular problems could be achieved. Unfortunately, therapeutic management has not yet improved significantly, but diagnostic investigations have become less invasive for most disorders. For the clinician, the most important problem is still realizing that the complains of the patient could be a symptom of a neuromuscular problem. This should be followed by a careful history and clinical examination, to achieve a topical diagnosis (from motoneuron to muscle) and if ever possible already a clinical suspicion of the diagnosis. Investigations like neurophysiological technics, lab investigations, forearm ischemic exercise test or even muscular biopsy might be helpful to achieve this goal. Nowadays verification of the diagnosis is done in most cases by genetic DNA testing or by specific immunohistochemical staining or enzyme determination in muscular biopsy. This diagnostic way enhances the importance of history and clinical examination even in today's modern neurology.

Acute leukoencephalopathy after inhalation of a single dose of heroin.

We describe extended and repeat magnetic resonance (MR) examinations in the case of a 16-year-old male who developed acute left-sided sensorimotor hemiplegia after a single dose of inhaled heroin. MRI revealed symmetrical hyperintense signals in T 2 -weighted images and massive diffusion disorders in the diffusion weighted images predominantly in parieto-occipital subcortical white matter and both ventral globi pallidi with preservation of U fibers and no brain oedema. MR spectroscopy data were compatible with combined hypoxic and mitochondrial damage resulting in axonal injury without demyelination. Normal values and variations had been obtained from spectra of five age-matched subjects. This is the first reported MR follow-up study of leukoencephalopathy occurring acutely after a first inhaled dose of heroin. We postulate that toxic spongiform leukoencephalopathy in heroin addicts may be the outcome of a complex mechanism directly triggered by heroin and causing mitochondrial as well as hypoxic injury in specific and limited areas of white matter.

Isotropic apparent diffusion coefficient mapping of postnatal cerebral development.

Diffusion-weighted imaging (DWI) allows us to image the motion of tissue water. This has been used to demonstrate acute ischaemia. Diffusion imaging is also sensitive to water movement along neuronal tracts. Our objective was to map brain maturation in vivo using maps of apparent diffusion coefficient (ADC). We studied 22 children without neurological disease aged between 2 and 720 days. MRI was performed at 1.5 tesla. Multislice single-shot echoplanar DWI was performed at b 0 and 1000 s/mm(2). ADC maps were generated automatically and measurements were performed in the basal ganglia, frontal and temporal white matter and the pons. There was a decrease over time in water diffusion in the areas examined, most marked in the frontal (0.887-1.898 x 10(-3) mm(2)/s) and temporal (1.077-1.748 x 10(-3) mm(2)/s)lobes. There was little change, after an initial decrease, in the basal ganglia (0.690-1.336 x 10(-3) mm(2)/s). There was a difference in water diffusion between the anterior (0.687-1.581 x 10(-3) mm(2)/s) and posterior (0.533-1.393 x 10(-3) mm(2)/s) pons. These changes correlate well with those observed in progressive myelination: the increased water content probably reflects incomplete myelination and the decrease with time in water motion reflects the increase in myelinated brain.

Neonatal Escherichia coli meningitis: spinal adhesions as a late complication.

We describe two boys who had severe spinal complications in adolescence after a favorable initial recovery from neonatal Escherichia coli meningitis. Due to spinal granulomatous adhesions, one boy died after an attempted scoliosis operation (high cord lesion). The other showed severe progressive neurological deterioration with spinal and cerebellar symptoms. Conclusion The severe complication of chronic arachnoiditis with spinal adhesion may occur many years after neonatal acute bacterial meningitis.

Cognitive impairments in patients with congenital nonprogressive cerebellar ataxia.

OBJECTIVE: To report neuropsychologic functions and developmental problems of patients with congenital nonprogressive cerebellar ataxia. BACKGROUND: Growing interest in cerebellar function has prompted closer attention to cognitive impairments in patients with cerebellar damage. METHODS: The authors studied 11 patients with nonprogressive congenital ataxia (NPCA) with Wechsler's intelligence testing, with additional tests of attention, memory, language, visual perception, and frontal functions. RESULTS: Seven of the 11 patients had an IQ of 60 to 92, with marked nonverbal deficits and subnormal to normal verbal performance (group A). Four patients had an IQ of 30 to 49 without pronounced profile asymmetry (group B). Four of the 7 group A patients had decreased alertness and sustained attention, but all had normal selective attention. Tests of frontal functions and memory yielded higher verbal scores than nonverbal scores. There was no deficit on the Aachener Naming Test (similar to the Boston Naming Test), because there were marked difficulties in the majority with visuoconstructive tasks and visual perception. Group B was significantly abnormal in almost all subtests, having a less prominent but similar profile. CONCLUSION: Patients with NPCA have significant cognitive deficits with an asymmetric profile and better verbal than nonverbal performance. Effects on nonverbal performance of longstanding deficits in visuospatial input during learning, the influence of impaired procedural learning, and asymmetric plasticity of the cerebral hemispheres may contribute to this uneven neuropsychological profile.