Fábio A. Nascimento

Diffuse idiopathic skeletal hyperostosis: A review.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic noninflammatory disease characterized by ossification of the entheses. Methods: This paper reviews the etiopathogenesis, epidemiology, clinical features, differential diagnosis, and treatment of DISH, based on current available literature. Results: Exact prevalence and incidence of DISH remains undetermined. Many external and genetic factors have been reported as being contributors to the pathogenesis of DISH. Current theories focus on the pathologic calcification of the anterior longitudinal ligament of the spine as the main physiopathological mechanism of disease. Clinical features are variable from monoarticular sinovitis to airway obstruction, and can be associated to systemic conditions. Comorbidities include obesity, hypertension, diabetes mellitus, hyperinsulinemia, dyslipidemia, and hyperuricemia according to a number of reports. Conclusions: DISH is a disease which involves the calcification of the anterior longitudinal ligament of the spine and can be associated with numerous clinical presentations and comorbidities.

Two definite cases of sudden unexpected death in epilepsy in a family with a DEPDC5 mutation

The DEPDC5 gene (OMIM #614191), mapped to 22q12.2-q12.3, encodes the DEP domain-containing protein 5. DEPDC5 has been associated with a variety of familial epilepsies, including familial focal epilepsy with variable foci, autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy, epileptic spasms, and cortical dysplasia.1–4 Notably, DEPDC5 has never been linked to increased risk of sudden unexpected death in epilepsy (SUDEP). We report a family with epilepsy due to DEPDC5 mutation and 2 definite cases of SUDEP within this family.

Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP)

OBJECTIVE To review studies on structural pulmonary and cardiac changes in SUDEP cases as well as studies showing pulmonary or cardiac structural changes in living epilepsy patients. METHODS We conducted electronic literature searches using the PubMed database for articles published in English, regardless of publication year, that included data on cardiac and/or pulmonary structural abnormalities in SUDEP cases or in living epilepsy patients during the postictal period. RESULTS Fourteen postmortem studies reported pulmonary findings in SUDEP cases. Two focused mainly on assessing lung weights in SUDEP cases versus controls; no group difference was found. The other 12 reported descriptive autopsy findings. Among all SUDEP cases with available descriptive postmortem pulmonary examination, 72% had pulmonary changes, most often pulmonary edema/congestion, and, less frequently, intraalveolar hemorrhage. Eleven studies reported on cardiac pathology in SUDEP. Cardiac abnormalities were found in approximately one-fourth of cases. The most common findings were myocyte hypertrophy and myocardial fibrosis of various degrees. Among living epilepsy patients, postictal pulmonary pathology was the most commonly reported pulmonary abnormality and the most common postictal cardiac abnormality was transient left ventricular dysfunction - Takotsubo or neurogenic stunned myocardium. SIGNIFICANCE Cardiac and pulmonary pathological abnormalities are frequent among SUDEP cases, most commonly pulmonary edema/congestion and focal interstitial myocardial fibrosis. Most findings are not quantified, with subjective elements and undefined interobserver reliability, and lack of controls such as matched epilepsy patients who died from other causes. Further, studies have not systematically evaluated potential confounding factors, including postmortem interval to autopsy, paramedic resuscitation and IV fluids administration, underlying heart/lung disease, and risk factors for cardiac or pulmonary disease. Prospective studies with controls are needed to define the heart and lung changes in SUDEP and understand their potential relationship to mechanisms of death in SUDEP.

OnabotulinumtoxinA for trigeminal neuralgia: a review of the available data

Trigeminal neuralgia (TN) patients may develop side effects from centrally acting drugs, have contraindications for neurosurgical procedures, or experience relapse during conventional therapies. OnabotulinumtoxinA (BoNT/A) has been reported to be effective for TN, although this finding has been challenged. An overview of the available evidence based on a narrative/qualitative analysis of the literature is presented. About 90% of patients who receive BoNT/A show an improvement, a higher figure than that reported for the placebo effect of BoNT/A for other headaches. Tolerability of BoNT/A is good, and its few side-effects are transient. The articles reviewed were mainly case reports, case series and open-label trials; however, randomized controlled trials have endorsed the efficacy of BoNT/A for TN. This evidence, together with a better understanding of the analgesic mechanisms of BoNT/A and its proven efficacy in treating other pain syndromes, supports the use of this toxin as a therapeutic option for TN.

Adult motor phenotype differentiates Dravet syndrome from Lennox-Gastaut syndrome and links SCN1A to early onset parkinsonian features

Distinguishing adult patients with Lennox‐Gastaut syndrome from those with Dravet syndrome is challenging. We have previously reported that patients with Dravet syndrome present a very peculiar motor phenotype. Here we sought to confirm that this association was not linked to the chronic use of antiepileptic drugs or the many lifetime seizures. To this aim, we studied 14 adult patients with Lennox‐Gastaut syndrome and 14 adults with Dravet syndrome because both conditions share similar seizure severity. We found that antecollis and parkinsonian gait were significantly more common in the Dravet group, thus suggesting that these features are part of the Dravet syndrome adult phenotype.

Hemophagocytic Lymphohistiocytosis After Initiation of Chemotherapy for Bilateral Adrenal Neuroblastoma.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome characterized by overactivation of the immune system. Although secondary HLH has been frequently associated with malignancies, this entity is rarely triggered by solid tumors, such as neuroblastomas. Herein, we describe a 14-month-old girl with a late diagnosis of bilateral adrenal neuroblastoma who developed HLH 6 days after the initiation of chemotherapy. On the basis of the large tumoral mass and the time of onset of her symptoms suggestive of HLH, we hypothesize that tumor cell destruction induced by chemotherapy drugs was the trigger to the development of hematophagocytic lymphohistiocytosis syndrome.

Phenytoin-induced isolated chronic, nocturnal dry cough.

We report a 72-year-old man with a four-year history of dyscognitive seizures (with occasional secondary generalization) who developed isolated, nocturnal dry cough immediately after being started on PO phenytoin. The cough was not accompanied by any other symptom or sign as his physical exam was completely normal. Further investigation with chest CT and spirometry was unremarkable. This symptom persisted for six months and did not resolve until we weaned him off of phenytoin. According to the Naranjo Adverse Drug Reaction Probability Scale, his cough was classified as being probably (score + 6) related to the use of this antiepileptic drug. To our knowledge, there has been only one study that reported phenytoin-triggered cough. It described a postoperative patient who developed cough and bronchospasm after receiving IV phenytoin. By reporting our case and discussing the literature on this specific topic, we have essentially two goals. First, we intend to remind clinicians that isolated persistent cough can be an adverse reaction to phenytoin. Second, we hope to encourage further studies that will be able to elucidate the association presented herein.

Spinocerebellar ataxias type 3 and 10: Onset and progression of ataxia during pregnancy and puerperium

SCA3 is characterized by gait ataxia, dysarthria and nystagmus. It is caused by mutations in the ATXN3/DMJ gene (OMIM#607047), which when mutated has an increased number of CAG repeats. SCA10, a rarer subtype, is characterized by ataxia with cerebellar atrophy and, in some case, seizures; dysarthria and dysphagia are common as the disease progresses. SCA10 is caused by expansion of ATTCT pentanucleotide repeats in the ATXN10 gene (OMIM#611150). Previous clinical observations showed that genetically determined neurodegenerative conditions e such as SCA10 and chorea-acanthocytosis e may be influenced by hormonal changes. In the same context, basic research studies showed that several hormone receptors are expressed in the cerebellum (including receptors for estrogen and progestogens), and that cerebellar function is strongly influenced by hormonal factors [1e4]. Based on the above-mentioned observations, we conducted a retrospective study to assess whether pregnancy and puerperium contribute to development and/or worsening of ataxia in women with SCA3 and SCA10. We included pregnant womenwith genetically confirmed SCA3 (n1⁄4 22) or SCA10 (n1⁄4 18) who were being regularly followed at our institution (Hospital de Clínicas/UFPR). Demographic and clinical variables included age, age of onset, change in ataxia during pregnancy/puerperium, and baseline assessment of ataxia severity using the Brazilian validated Scale for the Assessment and Rating of Ataxia (SARA) [5]. Scores for the SARA range from zero (no ataxia) to 40 (severe ataxia). This study was approved by our institutions ethics committee; all participants signed informed consents. Demographic and clinical data as well as results are shown in Table 1. Twelve patients with SCA10 (n1⁄4 12/18, 66.7%) and one patients with SCA3 (n1⁄4 1/22, 4.5%) reported either new onset or worsening ataxia during pregnancy (third trimester) or puerperium (within seven days of delivery) (p< 0.0001). Among the 12 patients with SCA10 who experienced new onset/worsening ataxia during pregnancy/puerperium, nine (n1⁄4 9/12, 75%) had new onset ataxia whereas three (n1⁄4 3/12, 25%) had worsening ataxia. The

The phenotype of bilateral hippocampal sclerosis and its management in “real life” clinical settings

There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics.

Spinal Dural Arteriovenous Fistula and Concomitant Intramedullary Spinal Lesion

2. Koenig E, Thron A, Schrader V, Dichgans J. Spinal arteriovenous malformations and fistulae: clinical, neuroradiological and neurophysiologic findings. J Neurol. 1989;236(5):260-266. 3. Kim DJ, Willinsky R, Geibprasert S, et al. Angiographic characteristics and treatment of cervical spinal dural arteriovenous shunts. AJNR Am J Neuroradiol. 2010;31(8):1512-1515. 4. Morris JM. Imaging of dural arteriovenous fistula. Radiol Clin North Am. 2012;50(4):823-839. Spinal Dural Arteriovenous Fistula and Concomitant Intramedullary Spinal Lesion Fábio A. Nascimento1, Peter Kan2, Lydia Sharp1, Jacob J. Mandel1