Hypertension, seizures, and epilepsy: a review on pathophysiology and management.

BACKGROUND: Epilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy. METHODS: We selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018. RESULTS: Renin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives. CONCLUSIONS: Current evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.

Cortical subarachnoid hemorrhage associated with reversible cerebral vasoconstriction syndrome after elective triplet cesarean delivery.

Reversible cerebral vasoconstriction syndromes (RCVS) comprise a group of disorders characterized by prolonged, but reversible vasoconstriction of the cerebral arteries, usually associated with acute-onset, severe, recurrent headaches, with or without additional neurological signs and symptoms. Various complications of this condition have been observed, such as cortical subarachnoid hemorrhages (cSAH), intracerebral hemorrhages, reversible posterior leukoencephalopathy, ischaemic strokes and transient ischaemic attacks. It is important to include RCVS in thunderclap headache differential diagnosis and among non-aneurismatic subarachnoid hemorrhage causes. In the past years, thanks to the major diffusion of new diagnostic tools such as magnetic resonance, computed tomography and digital subtraction angiography, RCVS have been demonstrated to be more frequent than previously thought. We report an illustrative case of a woman affected by a small cSAH, associated to RCVS, after elective triplet cesarean delivery. To our knowledge, this is the first case of cSAH associated to RCVS after a triplet pregnancy.

A case of secondary syphilis presenting as optic neuritis.

Neurosyphilis is still a significant medical problem in developing countries and syphilitic ocular manifestations are often not diagnosed due to the lack of typical characteristics. We describe the case of a 59-year-old homosexual man with a 1-month history of decreased vision acuity in his left eye who was diagnosed with neurosyphilis and received treatment with intravenous penicillin G (16 million units in divided daily doses), with great improvement of visual acuity and CSF examination findings. The interest of this case is not only represented by the unusually early ocular involvement, but also by the rapid evolution of the disease into the secondary stage in a man who had had one at-risk homosexual relationship only 3 months before the onset symptoms. We also support the view that the presence of ocular involvement in syphilitic patients is suggestive of involvement of the CNS and should be considered synonymous with neurosyphilis.

Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease.

We describe two patients with Parkinson's disease (PD) who developed clinical criteria of pathological gambling addiction in the setting of increased dopamine replacement therapy (levodopa and dopamine agonist medications). The second patient showed also signs of dopamine dysregulation syndrome, with an addiction to dopaminergic medication. Neither patients responded to the standard therapy for gambling behavior, but dramatically improved after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) and early postoperative withdrawal of dopaminergic therapy. The possible therapeutic role of subthalamic nucleus deep brain stimulation (STN-DBS) on such a disabling behavior needs to be investigated prospectively.

Sodium oxybate for idiopathic REM sleep behavior disorder: a report on two patients.

BACKGROUND: REM-sleep behavior disorder (RBD) therapy is based on small to medium-sized case series, as no large controlled clinical trials have been performed. The most used and widely recognized effective drugs are clonazepam and melatonin, with anecdotal reports on the potential benefit of other drug classes. METHODS: We report on two patients suffering from idiopathic RBD presenting with almost nightly complex and violent episodes, refractory to conventional drugs. Both patients, after informed consent, were treated off-label with sodium oxybate in add-on therapy. We followed up the patients in order to assess treatment efficacy by means of clinical interview, visual analog scales (VAS) for frequency and severity, Clinical Global Impression (CGI) improvement scale and efficacy index, video-polysomnography and at-home actigraphy. RESULTS: Sodium oxybate intake was well tolerated and effective in reducing the number and intensity of RBD episodes; patients reported no new traumatic episodes. Results were confirmed by bed-partner reports, VAS, CGI improvement scale and efficacy index, and at-home actigraphic monitoring, the latter showing a trend of improvement in nocturnal sleep quality and reduction in motor activity, compared to the baseline. Nevertheless, video-polysomnography did not show a clear beneficial effect on sleep-related electromyographic parameters. CONCLUSIONS: Our cases suggest that sodium oxybate can be an effective add-on option for the treatment of idiopathic RBD refractory to conventional therapies. The lack of improvement of polysomnographic parameters suggests caution in considering only polysomnographic data as endpoints in the assessment of the efficacy of therapies for RBD, and that long-term home-based assessment seems a promising tool.

The Role of the Serotonergic System in REM Sleep Behavior Disorder.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) can be induced by antidepressants, especially serotonin reuptake inhibitors (SSRI), thus a role of the serotonergic system in the pathogenesis of RBD has been proposed. However, the serotonergic system integrity in idiopathic RBD (iRBD) is still unknown. We aimed to study brain stem serotonergic system integrity, by means of (123)I-FP-CIT-SPECT, in a group of iRBD patients as compared to normal subjects. DESIGN: Single-center, prospective observational study. SETTING: University hospital. PATIENTS OR PARTICIPANTS: Twenty iRBD outpatients and 23 age-matched normal controls. MEASUREMENTS AND RESULTS: The diagnosis of RBD was determined clinically and confirmed by means of overnight, laboratory-based video-polysomnography. Both iRBD patients and normal subjects underwent (123)I-FP-CIT-SPECT as a marker of dopamine transporter (DAT) at basal ganglia level and of serotonin transporter (SERT) at brainstem and thalamus levels. (123)I-FP-CIT-SPECT images were analyzed and compared between iRBD patients and controls by means of both region of interest analysis at basal ganglia, midbrain, pons and thalamus levels, and voxel-based analysis, taking into account age and the use of SSRI as confounding factors. No difference in (123)I-FP-CIT-SPECT specific to nondisplaceable binding ratios (SBR) values was found between iRBD and normal subjects at brainstem and thalamus levels while iRBD patients showed lower SBR values in all basal ganglia nuclei (P < 0.0001) compared to controls. CONCLUSIONS: These results suggest that the serotonergic system is not directly involved in RBD pathogenesis while confirming nigro-striatal dopaminergic deafferentation in iRBD.

Ifosfamide encephalopathy and nonconvulsive status epilepticus.

BACKGROUND: Ifosfamide (IFX), an alkylating agent and isomer of cyclophosphamide, is used as a single agent or a component of multi-agent chemotherapy in the treatment of ovarian, testicular, head and neck cancers, sarcomas and lymphomas. Encephalopathy is manifested by cerebellar ataxia, confusional state, complex visual hallucinations, extrapyramidal signs, seizures, and mutism. CASE REPORTS: We report two patients with non-Hodgkin's lymphoma presenting with mutism and confusional state after IFX infusion. Nonconvulsive status epilepticus (NCSE) as the cause of confusion was diagnosed on the basis of EEG pattern and the apparent improvement following intravenous administration of diazepam. CONCLUSIONS: Electroencephalogram abnormalities during IFX treatment have been described but recordings are only available in six cases. In three of them, paroxysmal alterations warranted the diagnosis of NCSE; however, most cases of IFX encephalopathy might have associated NCSE.

Good functional outcome after prolonged postanoxic comatose myoclonic status epilepticus in a patient who had undergone bone marrow transplantation.

In anoxic coma, myoclonic status epilepticus and other nonreactive epileptiform patterns are considered as signs of poor prognosis. We report the case of a good recovery in a prolonged comatose myoclonic status epilepticus (MSE) after a cardiac arrest (CA) treated with mild therapeutic hypothermia (TH) in a patient who had undergone a bone marrow transplantation for Hodgkin's lymphoma. This case emphasizes the opportunity of performing an electroencephalogram (EEG) in the acute period after an hypoxic-ischemic insult and underlines the diagnostic difficulties between MSE and Lance-Adams syndrome, which classically occurs after the patient has regained consciousness, but can also begin while the patient is still comatose or sedated. Major problems in prognostication for postarrest comatose patients will also be pointed out.

Clarithromycin-induced neurotoxicity in adults.

Clarithromycin is a relatively new antibiotic of the macrolide family heralded for an improved side effect profile, dosing schedule, and microbiological activity relative to its parent compound, erythromycin. We review the literature on clarithromycin-induced neurotoxicity in adults and present an illustrative case. A total of 38 patients with clarithromycin-induced neurotoxicity have been reported. The average age of patients was 51.3 years (range: 19-87 years) with females comprising 52.6% of patients. Psychiatric illness was the most common comorbidity, while only two patients had renal failure. Clarithromycin had been prescribed for respiratory infections in most patients, and only two patients were receiving more than 1000 mg/day of antibiotic. The symptoms started 1 day to 10 days after starting clarithromycin (mean: 5 days). A total of 71% of patients were under treatment with concomitant medication, and eight patients were undergoing treatment with psychoactive drugs. Patients had a very good outcome after clarithromycin was discontinued, but medication with neuroleptics or benzodiazepine was required for 58% of patients in the acute phase. Only four patients underwent an electroencephalogram (EEG). Our illustrative patient was a 74-year-old woman with clarithromycin-induced delirium due to non-convulsive status epilepticus (NCSE). Her clinical symptoms and electroencephalogram (EEG) readings dramatically improved after discontinuation of clarithromycin. The mechanism underlying the central nervous system side effects remains unclear. We suggest including an EEG in the diagnostic procedures of patients under treatment with clarithromycin who develop features of neurotoxicity because an EEG can help to differentiate patients with psychiatric illness from those with encephalopathy or epilepsy. Because of the widespread use of clarithromycin, clinicians should be aware of its neurotoxicity. Early detection of clarithromycin-induced neurotoxicity and discontinuation of the drug may result in full recovery.

Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study.

Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated. Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

Nonconvulsive status epilepticus during cephalosporin therapy.

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.