Paraneoplastic limbic encephalitis with SOX1 and PCA2 antibodies and relapsing neurological symptoms in an adolescent with Hodgkin lymphoma.

BACKGROUND: Immune cross-reactivity between malignant and normal tissues causes the rare, so called paraneoplastic syndrome (PS). In approximately 60% of the patients, various onconeural antibodies are detectable in the cerebrospinal fluid (CSF) and are associated with typical tumour entities. METHODS: We report an unusual case of paraneoplastic limbic encephalitis (PLE) in a 17-year-old adolescent with classical Hodgkin lymphoma. RESULTS: He presented with a variety of neurologic and neuropsychiatric symptoms, profound B-symptoms and typical MRI findings including hyperintense lesions with contrast enhancement in the medial temporal lobe and limbic system. Under immunosuppressive therapy and subsequently chemotherapy the neurological situation only temporarily improved and worsened again after interruption of immunosuppression several times. Thus, multiple courses of multidrug immunosuppressive therapy were administered. To date, five years after initial presentation, the young man is able to walk with walking aids and orthoses and is still on oral prednisolone therapy. Analyses of the CSF and serum revealed anti SOX-1 antibodies at initial presentation but PCA-2 antibodies seven months after diagnosis. CONCLUSION: Neurologic and/or neuropsychiatric symptoms combined with typical MRI findings should raise the suspicion of PS and lead to further diagnostics for an underlying tumour even in children.

YouTube as a source of information for children with paroxysmal episodes.

Whereas to date the internet is a main source of information for many parents, there are no restrictions regarding data presentation. Thus, the aim of this study was to assess the quality of internet material concerning paroxysmal episodes.We rated videos on YouTube for several conditions like infantile spasms, absence seizures, Sandifer syndrome, sleep myoclonus, and shuddering attacks. Videos were classified into different categories of certainty of diagnosis according to expert opinion based on a 4 point Likert scale followed by calculation of interrater reliability. Also the quality of supplemental information was assessed, as well as whether videos were helpful from a neuropaediatrican's point of view in counselling patients and their parents.In sleep myoclonus, absences and infantile spasms correlation between title of videos and classification by expert opinion was good. There was more discrepancy with the videos concerning Sandifer syndrome and shuddering attacks. Interrater reliability was low for Sandifer syndrome, fair for absences, shuddering attacks and sleep myoclonus and moderate for infantile spasms. Some supplemental information was rated to be helpful but other information was found to be misleading or even unsettling for patients and their parents.We consider that video material on YouTube can generally not be considered as helpful for parents because of a significant disagreement between experts, even for the most well defined disorders in our study.

Pseudotumor cerebri in childhood and adolescence -- results of a Germany-wide ESPED-survey.

BACKGROUND: No valid epidemiological data on Pseudotumor cerebri (PTC) in childhood and adolescence are available. This national survey aims to raise awareness of the PTC in paediatrics and contribute to a better understanding of age-related characteristics. METHODS: Over 1 year (January-December 2008) new cases of PTC in childhood and adolescence from all paediatric hospitals in Germany were collected by the German Paediatric Surveillance Unit for rare diseases (ESPED). RESULTS: With a total of 61 cases, an annual incidence of 0.5 per 100 000 children <18 years was found. Children of all age groups were affected. A female preponderance and obesity was only found in adolescents. Clinical presentation was variable. Headaches represent the most common symptom affecting prepubertal children less frequently. A wide range of vision problems could be documented (papilledema, visual loss, double vision, visual field defects, disturbed colour and stereo vision). In 10 patients no papilledema was found. Comorbidities were reported in 23% of patients. 14 children gained remission after lumbar puncture without medication. Acetazolamide was the drug of choice, with relatively low dosages used. Escalation strategies were variable. 2 patients were treated invasively (sinus venous stent, LP shunt). CONCLUSION: PTC in childhood and adolescence appears to be as frequent as in the general population. Unspecific clinical characteristics and the broad spectrum of ophthalmologic findings emphasize the importance of a skilful neuroophthalmological investigation. Inconsistent therapeutic approaches are most likely due to a lack of diagnostic and therapeutic standards. Present diagnostic criteria and guidelines for the management of paediatric PTC do not sufficiently consider paediatric aspects.

Sedation of children during measurement of CSF opening pressure: lack of standardisation in German children with pseudotumor cerebri.

BACKGROUND: Diagnosis of pseudotumor cerebri (PTC) requires proper documentation of raised CSF opening-pressure. In childhood results may not be reliable due to insufficient sedation/analgesia or drug effects. We aimed to evaluate the current practice regarding pain and stress management in children undergoing lumbar puncture (LP) for pressure measurement. METHODS: A one-year survey was conducted involving 368 German paediatric departments. All children with newly diagnosed PTC should be reported. Details analyzed here included: age, sex, CSF opening pressure and type of procedural sedation and analgesia (PSA) during LP. RESULTS: 61 patients were analyzed, aged 6 months to 17 years. 29 patients (47%) did not receive any kind of PSA. In children receiving PSA the following regimens were used: Ketamine; Midazolam; Ketamine + Midazolam; Midazolam + Piritramide; Propofol; Profofol + Midazolam; general anaesthesia. CONCLUSION: Pain and stress management in children undergoing LP for CSF opening pressure measurement is often insufficient. Pain, stress and the variability of PSA regimen may be confounders of pressure measurement. In order to prevent false diagnoses of PTC and to obtain comparable results at different centers, a general consensus on PSA in children undergoing LP for CSF opening pressure measurements is required.

Infantile onset neurofibromatosis type 2 presenting with peripheral facial palsy, skin patches, retinal hamartoma and foot drop.

BACKGROUND: Neurofibromatosis type 2 (NF2) has long been regarded as an adult onset disease. However, it is now known that many NF2 patients present clinical signs and symptoms in early childhood. We here report an illustrative case of a male adolescent with an infantile onset clinical symptomatology. PATIENT: A 15-year-old male adolescent presented with a history of congenital peripheral facial palsy, amblyopia, a retinal "membrane", and weakness of the left lower limb. Clinical, electrophysiological, radiological, and molecular studies of the patient are shown. A peripheral axonal neuropathy of the left lower limb was found. Formerly unidentified retinal findings could be diagnosed as combined pigment epithelial, and retinal hamartoma (CPERH). In addition, two café au lait spots and a nodular skin tumour were found. Bilateral vestibular schwannoma finally led to the diagnosis of NF2, which could be genetically confirmed. CONCLUSIONS: NF2 can already become evident in infancy. While in adulthood tinnitus, hearing loss and vestibular symptoms are the classical signs, these are often absent in the paediatric group. Children rather have ocular symptoms, neurological problems such as cranial nerve palsies other than eighth nerve, limb weakness and skin manifestations as early clinical signs.

Obstruction of cerebral venous sinus secondary to idiopathic intracranial hypertension.

BACKGROUND: Whether cerebral venous sinus obstruction is a cause or consequence of idiopathic intracranial hypertension (IIH) is uncertain. METHODS AND RESULTS: Among the nine children with IIH, five showed stenosis (n = 5) and occlusion (n = 1) of cerebral venous sinus on cranial magnetic resonance imaging (n = 4) or conventional angiography (n = 1), respectively. Follow-up magnetic resonance imaging performed in four children showed complete regression of the venous pathology in one and partial regression in two of them. CONCLUSIONS: Our data demonstrate that cerebral venous sinus obstruction is frequent and frequently transient in pediatric IIH and suggest that stenoses may result from elevated intracranial pressure.

Diagnostic and therapeutic implications of neurological complications following paediatric haematopoietic stem cell transplantation.

Neurological complications are a relevant cause of morbidity and mortality after haematopoietic stem cell transplantation (SCT). We retrospectively analysed neurological complications of 165 paediatric patients who underwent SCT between 1996 and 2003. In all, 111 (67%) transplantations were allogeneic and 54 (33%) transplantations were autologous. Post-SCT neurological complications were seen in 24% of patients. They were seen in six children after autologous SCT and in 11 and 23 cases after allogeneic-related and -unrelated SCT. Neurological symptoms occurred between day +22 and +912 after transplantation and were classified into two groups. The first group (n=21) offered non-repetitive symptoms lasting less than 24 h without any cerebral imaging and cerebrospinal fluid(CSF) abnormalities. The second group (n=19) was characterized by progressive neurological symptoms, pathological MRI findings and/or abnormal results in CSF. Those with a progressive clinical course resulted from infections (n=10), drug toxicity (n=5), cerebrovascular events (n=2) and the central nervous system (CNS) relapse of the underlying disease (n=2). In particular, cerebral aspergillosis and toxoplasmosis after allogeneic unrelated SCT are a major challenge and are associated with a high mortality. In conclusion, our data suggest that patients presenting with progressive neurological symptoms after SCT require prompt diagnostic procedures and initiation in antimicrobial therapy in case of any findings suggestive of CNS infection.

Seasonal variation and atypical presentation of idiopathic intracranial hypertension in pre-pubertal children.

Idiopathic intracranial hypertension is an enigmatic disorder of elevated cerebrospinal fluid pressure. In adulthood, patients are typically obese women of childbearing age; however, in young children the clinical picture is strikingly different, indicating age-related differences in the aetiology of idiopathic intracranial hypertension. To investigate this phenomenon, we analysed the clinical details of 15 pre-pubertal children with the diagnosis of idiopathic intracranial hypertension. Evaluating the date of initial presentation, we discovered a distinct seasonal variation. Ten patients presented between November and March, thus coinciding with the typical season of paediatric viral and bacterial infections in Germany. Therefore, we suggest an association between intracranial hypertension and possibly concurrent infections in these children. Moreover, eight children presented only with ophthalmologic findings without any other obvious symptoms, raising questions regarding the incidence of undetected cases, particularly in this age group.

Antiepileptic treatment in paediatric oncology--an interdisciplinary challenge.

Epileptic seizures are a common and clinically relevant problem in paediatric oncology. Attributable to the heterogeneity of this group of patients and a number of possible comorbidities antiepileptic treatment in paediatric oncology poses a number of diagnostic and therapeutic challenges. This requires a close interdisciplinary approach to the seizing child or adolescent. A prompt and detailed diagnostic work-up is needed in every case in order to establish the diagnosis and, equally important, to detect secondary aetiological factors, e. g. epileptogenic drugs or any acute underlying pathology, such as metabolic or toxic encephalopathies, CNS-infections or cerebrovascular events. This might offer the opportunity for a specific causative treatment and thus prevent unnecessary long-term antiepileptic drug (AED) treatment. If AED treatment is initiated several aspects have to be taken into account. Most importantly, AEDs and chemotherapeutic drugs (CTDs) may interact. Depending on the comedication this may result in reduced tumour or seizure control or unexpected toxicity of AEDs or CTDs. Understanding these interactions will allow to anticipate clinically relevant adverse effects. AED may be further complicated by side-effects, some of them of particular concern for children or adolescents, such as cognitive effects, myelotoxicity, serious rashes, endocrinological disturbances, and many more. Beside critically questioning the need for AED treatment it is therefore important to prefer AED with a good safety-profile in this population. Enzyme-inducing and inhibiting AED should be avoided if possible. Preliminary studies indicate that gabapentin and levetiracetam may provide good options in terms of efficacy and safety. However, more properly designed clinical studies are warranted to raise the level of evidence for robust clinical recommendations. Until that time, clinicians will need to continue to question current policies and adapt their daily practice to evolving scientific data.