Pearls & Oy-sters: Frontal Lobe Syndrome Secondary to Cocaine-Induced Midline Destructive Lesions.

Cocaine-induced midline destructive lesions (CIMDL) are a rare complication of chronic intranasal cocaine use involving the centrofacial mucosal structures, often with nasal septum perforation and, in severe cases, involvement of neurocranial structures. Patients present with nasal obstruction, epistaxis, facial pain, nasal ulcerative lesions with crusting, and septal and palate perforation causing dysphagia and nasal reflux. CNS involvement is uncommon.We report a 47-year-old man with a history of nasal cocaine use who developed a subacute frontal syndrome secondary to cribriform plate destruction complicated by bilateral frontal lobe empyema and abscesses and extensive white matter involvement. The frequent presence of serum antineutrophil cytoplasmic antibodies (ANCA) in CIMDL makes this uncommon presentation challenging to differentiate from localized granulomatosis with polyangiitis. While ANCA antibodies may play a role in CIMDL, immunosuppression is not indicated and may lead to iatrogenesis.CIMDL should be considered in patients with isolated frontal lobe syndrome. Eliciting a history of cocaine use and obtaining toxicologic studies are essential in the diagnosis of CIMDL.

Long-term effectiveness and tolerability of galcanezumab in patients with migraine excluded from clinical trials: real world evidence of 1055 patients with 1 year follow-up from the Galca-Only registry.

BACKGROUND: Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. METHODS: Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. RESULTS: We enrolled 1055 patients, aged 50 (IQR: 42-58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3-5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8-12; 60.9%, 48.8% and 24.6% between weeks 20-24; and 59.7%, 48.3% and 24.6% between weeks 44-48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469-0.817) and patient's age (OR: 1.016; 95%CI: 1.005-1.026) were associated with 50% response at weeks 20-24. The variables that were associated with a higher reduction of headache days between weeks 20-24 were patient's age (0.068; 95% CI: 0.018-0.119) and headache days per month at baseline (0.451; 95% CI: 0.319-0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626-0.538) and daily headache at baseline (-2.718; 95% CI: -4.58-0.869) were associated with fewer reduction in the number of headache days between weeks 20-24. CONCLUSION: This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.

Adverse reactions to antipsychotics in Parkinson disease: an analysis of the Spanish pharmacovigilance database.

PURPOSE: Although antipsychotics are well known for causing a plethora of adverse drug reactions (ADRs), the main concern when used to treat psychosis in Parkinson disease (PD) has traditionally been motor function worsening. The limited number of patients included in clinical trials contributes to underreport less common ADR. The aims of this study were to describe ADR to antipsychotics occurring in patients with PD notified to the Spanish Pharmacovigilance System and to contrast them with published reports. METHODS: All notifications from the Spanish Pharmacovigilance System for the last 30 years (1984-2014) where an antipsychotic was considered suspicious of the ADR in patients who were also on dopaminergic therapy were reviewed. In addition, a systematic search of MEDLINE (1966-2014) was conducted with the following Medical Subject Headings (MeSH) terms: "Parkinson disease" and "antipsychotic agents" or "psychotic disorders" and "drug-related side effects" or "adverse reactions." RESULTS: Forty-four notifications were selected for evaluation. Quetiapine was the most frequently implicated drug since 2002, and previously clozapine was the drug implied in higher number of notifications. The most severe ADR was neuroleptic malignant syndrome, which was described in 5 patients (3 cases related to quetiapine, one to haloperidol, and another to olanzapine). CONCLUSIONS: Some previously unreported ADRs caused by antipsychotic drugs in patients with PD have been described for the first time in this study, although there are in general well-known antipsychotic adverse effects. It is remarkable that some notifications involve the use of drugs not recommended in these patients.

Pearls & Oy-sters: chronic mumps meningoencephalitis with low CSF glucose and acute hydrocephalus in an adult.

Chronic lymphocytic meningoencephalitis with low glucose and increased adenosine deaminase (ADA) levels in the CSF together with hydrocephalus represents a diagnostic challenge of varied etiology and only seldom is due to a viral (mumps) infection.

Intracerebral hematoma complicating herpes simplex encephalitis.

OBJECTIVES: To describe two patients who developed an intracranial hematoma as a complication of temporal lobe encephalitis due to herpes simplex type 1 virus, and to review the literature. PATIENTS AND METHODS: The first patient, a 45-year-old woman developed a brain hematoma in the location of the encephalitic lesion on day 9 after the onset of herpes simplex encephalitis (HSE) that required surgical evacuation. The second patient, a 53-year-old woman was being treated for HSE; on day 8 after admission a temporal lobe hematoma with midline shift was disclosed due to persistent headache. Both patients survived but were left with sequelae. We conducted a PubMed/MEDLINE search from 1986 to April 2013 on this topic. RESULTS: We have found 20 additional cases reported in the literature and review their characteristics. Hemorrhage was present on admission in 35% of pooled patients, and consistently involved the area of encephalitis. Clinical presentation of intracranial hemorrhage overlapped the encephalitic symptoms in two-thirds of the patients. Half of patients underwent surgery. Overall, mortality rate was low (5.2%), and half of patients fully recovered. CONCLUSIONS: Intracranial bleeding, although infrequent, can complicate the evolution of herpes simplex encephalitis and should be borne in mind since its presence may require neurosurgery. Although its presentation may overlap the encephalitic features, the lack of improvement or the worsening of initial symptoms, particularly during the second week of admission, should lead to this suspicion and to perform a neuroimaging study.

Migraine, stroke and epilepsy: underlying and interrelated causes, diagnosis and treatment.

OPINION STATEMENT: Migraine, epilepsy and stroke are highly prevalent neurological disorders, often comorbid. They share diverse pathophysiological mechanisms that explain the use of similar drugs on certain occasions (i.e., the use of antiepileptic drugs in migraine prevention). Migraine with aura represents a risk for ischemic stroke, and avoiding contraceptives, tobacco use, and ergot alkaloids should be advised in those patients. Epilepsy bears a bidirectional relationship with headache. Only three entities are considered as seizure-related headaches: migraine-triggered seizure (migralepsy), hemicrania epileptica, and post-ictal headache. Topiramate (100-200 mg daily) and valproic acid (500-1,000 mg daily) are first-line drugs in migraine prevention, while older antiepileptics have no use in this setting. Stroke is the most common cause of symptomatic epilepsy in the adult. Therapy with lamotrigine, gabapentine, and levetiracetam is advised in late-onset (2 weeks after stroke) stroke-seizures, while early-onset seizures usually do not require therapy.

The ocular ischemic syndrome.

The ocular ischemic syndrome represents a serious blinding condition due to retinal ischemia secondary to hemodynamically significant carotid artery stenosis. However, this condition has received little attention in the neurological literature and is likely underdiagnosed. We here describe a patient with bilateral severe carotid stenosis and progressive visual loss due to ocular ischemia. The best management for this condition remains controversial and should be established by including these patients into randomized trials of carotid surgery.

Soluble urokinase receptor (uPAR, CD 87) is present in serum and cerebrospinal fluid in patients with neurologic diseases.

BACKGROUND: The receptor for urokinase plasminogen activator (uPAR) promotes invasion by neoplastic or inflammatory cells by focusing proteolysis of urokinase to the cell surface. In pathologic conditions, soluble forms of the receptor (suPAR) are released, and activate cell receptors to promote chemotaxis. In the CNS, suPAR and other components of the plasminogen activation system (PAS) could be associated with an increase of the blood-brain barrier (BBB) permeability and subsequent neural damage. OBJECTIVE: To detect suPAR in the serum and cerebrospinal fluid (CSF) of patients with diverse neurologic conditions. PATIENTS AND METHODS: Serum and CSF from 121 patients with cancer, bacterial and viral infection, stroke, demyelinating disease and peripheral neuropathy were examined for the presence of suPAR. RESULTS: suPAR was elevated in the serum of patients with paraneoplastic syndromes, and carcinomatous meningitis and infections, but less in stroke and demyelinating disease patients. CSF suPAR was present in the cancer and CNS infection groups, but not in the other groups. The levels of serum and CSF suPAR were correlated, and CSF suPAR correlated with the albumin index. CONCLUSIONS: suPAR is present in serum and CSF of patients with carcinomatous meningitis, paraneoplastic disorders and bacterial and viral infection of the CNS. suPAR could be associated with BBB disruption and with promotion of CNS invasion by chemotactically active cells, macromolecules, and microbes.