Spontaneous Intracranial Hypotension: An Uncommon Cause of Postural Vestibulocochlear Symptoms.

Spontaneous intracranial hypotension is an uncommon but increasingly recognized condition characterized by an orthostatic headache secondary to low cerebrospinal fluid pressure. Vestibulocochlear symptoms are common but rarely the only presenting feature and can be challenging to differentiate from Meniere's disease. We present a case series that highlights the common vestibulocochlear symptoms and a review of the literature to increase awareness amongst otolaryngologists and highlight the path to diagnosis and management of this condition.

Recognition and epileptology of protracted CLN3 disease.

OBJECTIVE: This study was undertaken to analyze phenotypic features of a cohort of patients with protracted CLN3 disease to improve recognition of the disorder. METHODS: We analyzed phenotypic data of 10 patients from six families with protracted CLN3 disease. Haplotype analysis was performed in three reportedly unrelated families. RESULTS: Visual impairment was the initial symptom, with onset at 5-9 years, similar to classic CLN3 disease. Mean time from onset of visual impairment to seizures was 12 years (range = 6-41 years). Various seizure types were reported, most commonly generalized tonic-clonic seizures; focal seizures were present in four patients. Progressive myoclonus epilepsy was not seen. Interictal electroencephalogram revealed mild background slowing and 2.5-3.5-Hz spontaneous generalized spike-wave discharges. Additional interictal focal epileptiform discharges were noted in some patients. Age at death for the three deceased patients was 31, 31, and 52 years. Molecular testing revealed five individuals were homozygous for c.461-280_677 + 382del966, the "common 1-kb" CLN3 deletion. The remaining individuals were compound heterozygous for various combinations of recurrent pathogenic CLN3 variants. Haplotype analysis demonstrated evidence of a common founder for the common 1-kb deletion. Dating analysis suggested the deletion arose approximately 1500 years ago and thus did not represent cryptic familial relationship in this Australian cohort. SIGNIFICANCE: We highlight the protracted phenotype of a disease generally associated with death in adolescence, which is a combined focal and generalized epilepsy syndrome with progressive neurological deterioration. The disorder should be suspected in an adolescent or adult patient presenting with generalized or focal seizures preceded by progressive visual loss. The common 1-kb deletion has been typically associated with classic CLN3 disease, and the protracted phenotype has not previously been reported with this genotype. This suggests that modifying genetic factors may be important in determining this somewhat milder phenotype and identification of these factors should be the subject of future research.

The other side of the leaf: Seizures associated with synthetic cannabinoid use.

There has recently been a marked rise in the medicinal use of cannabis for epilepsy and multiple other conditions. While seizures have been reported in association with synthetic cannabinoids, the clinical features and prognosis have not been studied. Thirty patients with a history of seizures occurring within 24 h of synthetic cannabinoid use were identified from a first seizure clinic database in Perth, Western Australia between 2011 and 2016. Eight had a prior history of seizures, three related to synthetic cannabinoid use, with an additional three patients having risk factors for seizures. The presenting event was a tonic-clonic seizure in 27 patients (90%). "Kronic" was the synthetic cannabinoid used by 16 patients. Absorption was via smoking in all cases, with seizures occurring within 30 min of inhalation in 14 patients (46%). Electroencephalography (EEG) showed epileptiform abnormalities in 11%, and neuroimaging revealed epileptogenic lesions in 12%. Nine of 24 patients with follow-up had subsequent seizures, occurring in the setting of further synthetic cannabinoid use in two patients. This seizure recurrence rate is similar to seizures provoked by other acute systemic insults. In conclusion, smoking of some synthetic cannabinoids is associated with seizures, and this may relate to an intrinsic proconvulsant effect.

The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain.

Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional "denervation" which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.

Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy.

PURPOSE: Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). METHOD: In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. RESULTS: While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. CONCLUSION: Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Vertebral artery dissection as a cause of cervical radiculopathy.

The acute onset of neck pain and arm weakness is most commonly due to cervical radiculopathy or inflammatory brachial plexopathy. Rarely, extracranial vertebral artery dissection may cause radiculopathy in the absence of brainstem ischemia. We describe a case of vertebral artery dissection presenting as cervical radiculopathy in a previously healthy 43-year-old woman who presented with proximal left arm weakness and neck pain aggravated by movement. Cervical magnetic resonance imaging (MRI) and angiography revealed dissection of the left vertebral artery with an intramural hematoma compressing the left C5 and C6 nerve roots. Antiplatelet treatment was commenced, and full power returned after 2 months. Recognition of vertebral artery dissection on cervical MRI as a possible cause of cervical radiculopathy is important to avoid interventions within the intervertebral foramen such as surgery or nerve root sleeve injection. Treatment with antithrombotic agents is important to prevent secondary ischemic events.

Postprocedural inflammatory inferior alveolar neuropathy: an important differential diagnosis.

Lingual or inferior alveolar nerve (IAN) injury after dental procedures may result from direct trauma or local anesthetic agent and presents with immediate onset of typically nonprogressive symptoms, including pain and sensory changes. We report a case of delayed-onset pain and progressive sensory symptoms after IAN block for amalgam restoration. A 54-year-old man presented with progressive right-sided facial pain 48 hours after IAN block for amalgam restoration, followed 1 week later by hypoesthesia and allodynia in IAN distribution. The presentation is more consistent with inflammatory neuropathy, as is well recognized in brachial plexopathy. Imaging was used to exclude local and central causes, following which the clinical diagnosis was made. Inflammatory neuropathies may be distinguished from iatrogenic causes on the basis of delayed symptom onset, early severe pain, and progressive sensory symptoms. Awareness of this condition is important, because early steroid therapy followed by medications for neuropathic pain may provide benefit.

Enduring efficacy of Botulinum toxin type A injection for refractory anterior knee pain.

PURPOSE: To examine long-term outcomes of Botulinum toxin type A (BoNT-A) injection to vastus lateralis (VL) for refractory anterior knee pain (AKP). METHODS: Two cohorts (private clinic referrals and previous research participants) injected with BoNT-A for AKP by one neurologist were surveyed retrospectively. Primary outcomes were self-reported benefit, duration of symptom relief, and knee surgery post-injection. Secondary outcomes were changes in utilization of medication/physiotherapy treatment, AKP symptoms and activity limitation. RESULTS: Overall, average symptom duration was 76 months (SD 98). Responses were available from 46 of 53 private patients. Thirty-eight reported benefit from injection, which was ongoing in 29. Average benefit was 25 months (SD 21). Nine individuals reported symptom recurrence after an average of 14 months (SD 21). Ten had knee surgery post-injection; six of whom had not benefitted from BoNT-A injection. Nineteen of 23 previous research participants were contactable. Initially, all responded favorably to injection. Symptomatic benefit, with an average duration of 44 months (SD 20), persisted in 15. Two subjects proceeded to surgical intervention. CONCLUSIONS: A single BoNT-A treatment to VL led initially to improved function and relief of knee-related symptoms in 57 of 65 individuals. Improvements were sustained at follow-up, with an average benefit of 34 months (SD 25) post-injection, in 44 of 57 cases.

Treatment of refractory anterior knee pain using botulinum toxin type A (Dysport) injection to the distal vastus lateralis muscle: a randomised placebo controlled crossover trial.

OBJECTIVES: This randomised controlled crossover trial examined the efficacy of botulinum toxin type A (BoNT-A) injection, plus an exercise programme, to remediate chronic anterior knee pain (AKP) associated with quadriceps muscle imbalance. METHODS: 24 individuals with refractory AKP received either BoNT-A (500 U Dysport) or the same volume saline injection to the vastus lateralis (VL) muscle and performed home exercises focusing on re-training the vastus medialis (VM) muscle. All subjects were offered open-label injection at 12 weeks. Knee-related disability (anterior knee pain scale; AKPS) and activity-induced pain (10 cm visual analogue scale) at 12 weeks were the primary outcomes. Peak isometric extensor force was recorded and normalised VL:VM ratios were derived from simultaneous surface electromyography. Self-reported pain and disability measures were collected at six time points to a mean of 20±8 months. RESULTS: 14 subjects received BoNT-A and 10 placebo injection. Improvement at 12 weeks was significantly greater for BoNT-A compared with placebo-injected subjects for the AKPS (p<0.03), pain on kneeling (p<0.004), squatting (p<0.02) and level walking (p<0.04). At week 12, five placebo subjects crossed over to open-label injection. At 24 weeks, 16 of 19 BoNT-A-injected and two of the remaining five placebo-injected subjects were either satisfied or very satisfied with treatment outcomes. Improvements were maintained in 11 of 14 BoNT-A-injected and two of five placebo subjects available at longer-term follow-up. CONCLUSION: BoNT-A injection produced a greater reduction in pain and disability than placebo injection in carefully selected patients with chronic AKP related to quadriceps muscle imbalance.

Prolonged vastus lateralis denervation after botulinum toxin type A injection.

Intramuscular injection of botulinum toxin (BoNT) produces reversible blockade of neuromuscular transmission. In animal experimental models, recovery begins within four weeks and is usually complete by twelve weeks. We present evidence of prolonged denervation following BoNT injection of the vastus lateralis (VL) muscle to correct quadriceps muscle imbalance in patients with chronic anterior knee pain. Needle electromyography data were obtained from 10 subjects who had received a single BoNT treatment 5 to 19 months earlier as part of a clinical trial. Insertional and spontaneous activity, recruitment, and motor unit action potentials were examined. Clear differences between the injected and non-injected VL muscles, which correlated with the time since injection, were identified in all subjects. All 10 subjects studied with needle EMG showed evidence of persisting denervation in the BoNT-A injected VL muscle beyond the period of neuromotor recovery expected from animal experimental studies.

Prognostic implications of seizure recurrence in the first year after anterior temporal lobectomy.

PURPOSE: Seizure recurrence after anterior temporal lobectomy (ATL) incites concerns of whether seizures will eventually be successfully controlled. Our study evaluated the prognostic significance of seizure recurrence in the first year after ATL. METHODS: The postoperative courses of 175 consecutive patients who had undergone ATL and had > or =2 years of follow-up were studied. Recurrence was considered early if the first seizure occurred within 7 days after ATL and late if it occurred >7 days after ATL. Recurrent seizures were considered provoked when precipitating factors were present, such as interruption of antiepileptic drug (AED) intake. Subsequent outcome was determined at terminal follow-up. RESULTS: Percentage of excellent outcome was comparable between patients whose initial recurrent seizures were auras or simple partial seizures and patients without seizure recurrence in the first year (86.7 vs. 93.1%; p > or = 0.05). However, percentage of excellent outcome was less when the initial recurrent seizure was complex partial, either with or without secondary generalization (44.8%; p < or = 0.01). Outcome was not different between early and late seizure recurrence (excellent in 41.7 vs. 55.7%; p > or = 0.05). Nonetheless, patients with either early or late seizure recurrence were less likely to have excellent outcome than were patients with no seizure recurrence in the first year (p < or = 0.001). Percentage of excellent outcome was best when patients were seizure free in the first year (93.1%), intermediate when initial recurrent seizure was provoked (72.0%), and worst when unprovoked (27.8%) (p < or = 0.001). CONCLUSIONS: In the first postoperative year, the type of initial recurrent seizure, whether aura or complex partial and whether provoked or unprovoked, is associated with long-term prognosis in seizure control after ATL. The timing of the initial seizure recurrence is not as important.