Sibila Nanković

Vagus nerve stimulation in Lafora body disease.

Introduction Lafora body disease (LBD) is a rare autosomal recessive disorder characterized by progression to inexorable dementia and frequent occipital seizures, in addition to myoclonus and generalized tonic–clonic seizures (GTCSs). It belongs to the group of progressive myoclonus epilepsies (PMEs), rare inherited neurodegenerative diseases with great clinical and genetic differences, as well as poor prognosis. Since those patients have a pharmacoresistant disease, an adjunctive treatment option is vagus nerve stimulation (VNS). To date, there are four reported cases of the utility of VNS in PME — in Unverricht–Lundborg disease (ULD), myoclonic epilepsy with ragged-red fibers (MERRF), Gauchers disease, and in one case that remained unclassified. Case presentation A 19-year-old male patient had progressive myoclonus, GTCSs that often progressed to status epilepticus (SE), progressive cerebellar and extrapyramidal symptomatology, and dementia, and his disease was pharmacoresistant. We confirmed the diagnosis of LBD by genetic testing. After VNS implantation, in the one-year follow-up period, there was a complete reduction of GTCS and SE, significant regression of myoclonus, and moderate regression of cerebellar symptomatology. Conclusion To our knowledge, this is the first reported case of the utility of VNS in LBD. Vagus nerve stimulation therapy may be considered a treatment option for different clinical entities of PME. Further studies with a larger number of patients are needed.

Primary diffuse leptomeningeal gliomatosis: early diagnostic signs

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare malignant condition of meninges with only 83 cases reported in the literature so far. It is caused by glial cell infiltration, without evidence of a primary brain or spinal cord tumour. In this letter, we point out the importance of early recognition of clinical and neuroradiological signs of the disease and radical oncological treatment.

Oxcarbazepine-induced jerky see–saw nystagmus

A 43-year-old female presented to the emergency department because of dizziness, drowsiness and generalized urticaria that occurred the previous day. Patient’s history revealed protracted delivery with neonate asphyxia, following which she had been diagnosed with epilepsy at age 7 when she experienced her first generalized tonic–clonic seizure. Her MRI showed ulegyria and hypoxic–ischaemic changes characteristic for perinatal damage. Her last visit to an epilepsy clinic was 18 days before. At that time a change in her therapy was made with gradual initiation of oxcarbazepine (start dose of 300 mg QD in the evening for 5 days, than 300 mg BID for 5 days, than 300 mg in the morning and 600 mg in the evening for 5 days) and tapering of levetiracetame. Her therapy, at the time of her presentation to the emergency department, was (in total daily doses): oxcarbazepine 900 mg, sodium valproate 1,000 mg, levetiracetame 750 mg, clonazepam 4.5 mg, lamotrigine 100 mg. Neurologic examination revealed a jerky see–saw nystagmus (SSN) more pronounced on the right eye (Video 1). Brain CT scan was normal. Oxcarbazepine and lamotrigine were discontinued and carbamazepine was gradually introduced. The carbamazepine was chosen because this drug controlled her seizures very well in the past, however, pediatric neurologist chose to switch from carbamazepine to levetiracetame at one point. On follow-up, a week later, she did not have nystagmus and did not experience dizziness and drowsiness any more but still had residual urticaria on her face and neck. SSN is a torsional–vertical nystagmus in which one eye elevates and intorts, while the other depresses and extorts. Jerky SSN is reportedly caused by lesions in the chiasmal or parasellar area thus resulting from disruption of the visual pathway [1]. However, SSN was described in association with vascular and inflammatory lesions of the rostral midbrain, pons and cerebellum [1, 2]. Based on these reports, SSN can result from dysfunction of the medial longitudinal fasciculus (MLF) that coordinates input to the oculomotor and trochlear nuclei from the vestibular nuclei [2]. One of the most common side–effects of oxcarbazepine therapy is nystagmus and it is related to its mono-hydroxyderivative levels in serum [3]. The therapeutic effect of oxcarbazepine results from its effect of blocking neural ion channels. We hypothesize that the same effect caused SSN in our patient blocking neurons that are part of the MLF. As nystagmus is a well-described side–effect of antiepileptic therapy and given the fact that nystagmus in our patient commenced on initiation and disappeared on discontinuation of oxcarbazepine, we report on a yet undescribed case of jerky SSN caused by oxcarbazepine.

A case of adult-onset poststreptococcal opsoclonus–myoclonus syndrome

Opsoclonus–myoclonus syndrome (OMS) is a rare neuroinflammatory disease of paraneoplastic, parainfectious or idiopathic origin, characterized by opsoclonus, myoclonus, ataxia, as well as behavioral and sleep disorders. OMS is a rare disorder that appears in 1 in a million individuals worldwide. It usually affects infants and young children. In approximately 50% of affected children, a tumor of embryonic nerve cells (neuroblastoma) is responsible for the symptoms associated with OMS. In other cases, the disorder has been designated “idiopathic” or attributed to various— mostly—viral infections (Coxsackie virus B3 or St. Louis encephalitis virus) or bacterial infections (Streptococcus) [1, 2]. We present a case of a 22-year-old girl that was admitted to our hospital due to opsoclonus with rapid, involuntary, horizontal and vertical, conjugate fast eye movements, mild myoclonic jerks of eyelids, upper and lower limbs, and mild ataxia. Extensive diagnostic evaluation was performed. Her routine investigations of laboratory tests, including thyroid hormones were normal. Erythrocyte sedimentation rate, C-reactive protein and other immunological tests (antinuclear antibody, antineutrophil cytoplasmic antibodies, antidsDNA antibodies, C3 and C4-complement, serum immunoelectrophoresis) were negative, as well as oncomarkers, paraneoplastic and antiganglioside antibodies. Swab of the posterior pharynx revealed Streptococcus pyogenes (group A). Patient did not have signs of pharyngitis. Antistreptolysin O (ASO) titer was 653 IU/ml. Tests for detection of viral markers for cytomegalovirus, Epstein–Barr virus, herpes simplex viruses type 1 and 2, varicella-zoster virus, human immunodeficiency virus, hepatitis B and C virus were negative. Molecular-genetic analysis for spinocerebellar ataxia type 1, 2, 3, 6, and 7, MELAS (mitochondrial myopathy, encephalopathy lactic acidosis, and stroke-like) syndrome, myoclonic epilepsy with ragged red fibers, Unverricht–Lundborg disease (EPM1) and Lafora disease (EPM2A or EPM2B) was normal. Anti-neuroleukin antibodies, urinary vanillylmandelic acid and homovanillic acid were not determined in our patient. Anti-Ri and anti-Hu antibodies were negative. Cerebrospinal fluid analysis was within normal limits. Electroencephalogram showed right temporoparietal lateralisation and left focal abnormalities with occasional generalized spike-and-wave discharges. Brain magnetic resonance imaging 3-Tesla was normal. Positron emission tomography showed increased glucose metabolism in the tonsils and sublingual glands. Electromyoneurography found a mild sensory polyneuropathy. Following diagnostic evaluation, we have made the diagnosis of poststreptococcal OMS and administered intravenous immunoglobulin (IVIG) at doses of 0.4 g/kg given on 5 consecutive days, with oral penicillin V for 10 days and then intramuscular benzathine penicillin G, which resulted in clinical improvement and gradual normalization of neurological status. We have also started antiepileptic therapy with levetiracetam and clonazepam. The treatment of IVIG continued till today once a month, with remission of the disease. Intramuscular benzathine penicillin G was introduced every month for a year. 2 years since the beginning of the treatment, the ASO titer decreased (304 IU/ml). Five years since the beginning of the treatment, the disease is still in remission. The immunopathogenesis of OMS is poorly understood. There appears to be humoral and cell-mediated immune mechanisms involved both in paraneoplastic and idiopathic syndromes [3]. In many cases the symptoms are reversible * Ivana Cajic ivana345@gmail.com

Ritscher – Schinzel Syndrome – 3C (Cranio-Cerebello-Cardiac) Syndrome: Case Report

Ritscher-Schinzel or “cranio-cerebello-cardiac“ (3C) syndrome is a rare autosomal recessive syndrome characterized by craniofacial, cerebellar and cardiac anomalies. Central nervous system anomalies include Dandy-Walker malformation, cerebellar vermis hypoplasia and enlargement of the cisterna magna. Ritscher-Schinzel syndrome is listed as a very rare disease by the Office of Rare Diseases (ORD) of the National Institutes of Health and so far only about 30 cases are reported all over the world, mostly from North America and Europe. We present a case of young male patient born in 1972, who was, soon after his birth, operated due to cleft palate, and afterwards because of ventricular septal defect. From 1989 he has been treated due to epilepsy with signs of psychomotor retardation. In 2008 brain CT revealed Dandy-Walker malformation. In March 2009 he was hospitalized in the Department of Neurology of the University Hospital Centre Zagreb, where brain MRI confirmed described malformation with enlargement of the posterior fossa by cystic formation and aplasia of the caudal part of cerebellar vermis, as well as extensive bilateral subependymal areas of gray matter heterotopia. He clinically presented with craniofacial dysmorphism, syndactylia of 1st and 2nd finger on his right foot, flexion contractures of the distal phalanges of 2nd and 3rd finger on the both hands, and thoracic scoliosis. X-ray examination also revealed hypoplasia of the 1st right rib, congenital block of C6-C7 vertebral bodies and sinistroconvex scoliosis of thoracal segment. Based on clinical examination, neuroradiologic and radiologic diagnostic procedures we believe that our patient fills all necessary criteria for the diagnosis of Ritscher-Schinzel syndrome. So far he is the oldest patient described in the literature, and first described patient in Croatia.