Heather Angus-Leppan

The spinal cord processing of input from the superior sagittal sinus: pathway and modulation by ergot alkaloids

The effects of ergot alkaloids on field potentials and unit responses produced in the upper cervical spinal cord by stimulation of the superior sagittal sinus (SSS) were examined in 57 anesthetized cats. Electrical stimulation of the SSS produced field potentials and single-unit responses at latencies of 5-20 ms. Field potentials were abolished by section of the first division of the trigeminal nerve but were unaffected or increased by section of the upper cervical nerves. Field potentials were reduced or abolished by intravenous injection of ergotamine or dihydroergotamine (DHE). The evoked response of 41 units (34.4%) were suppressed by either i.v. or iontophoretic administration of ergotamine, DHE or ergometrine. The results suggest that ergot alkaloids exert an effect at a spinal cord relay centre which receives trigeminally mediated input from cranial blood vessels.

Diagnosing epilepsy in neurology clinics: a prospective study.

The certainty of the initial diagnosis of epilepsy was assessed prospectively by one neurologist in outpatients. One hundred and fifty-eight consecutive referrals with loss of consciousness or possible epilepsy were seen. The relative contributions to the initial diagnosis from the referral letter, history taking in clinic, physical examination, and investigation were compared. There was a referring diagnosis in 28.5%. The neurologist reached a diagnosis in 87% of the 158 cases: in 43% epilepsy, 25% syncope, 12% non-epileptic seizures and in 7% other diagnoses. There was a low correlation between referral and specialist diagnosis. Physical examination did not change the diagnosis in any patient. Investigations changed the diagnosis in one patient. Neuro-imaging revealed a relevant abnormality in 12/43 (27.9%) scanned. The yield from EEG was 7/25 (28%), but the EEG changed the diagnosis in only one case. Cardiac testing confirmed the type of syncope in 2/47 (4.3%) of patients. Blood tests did not contribute to the diagnosis in any patient. The neurology consultation significantly increased diagnostic certainty. The diagnosis of epilepsy remains largely clinical. It is important that patients are aware of this prior to investigation.

Convergence of occipital nerve and superior sagittal sinus input in the cervical spinal cord of the cat

Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches.

Autoantibodies in sporadic Creutzfeldt-Jakob disease.

IMPORTANCE The diagnosis of autoimmune and neurodegenerative conditions can be unclear. Treatments such as removing the associated tumor, if present, and immunosuppression can halt or often reverse the progression of autoimmune conditions, but there is no curative treatment for neurodegenerative conditions. The presence of autoantibodies can sometimes be misleading. This report illustrates potential difficulties in differentiating autoimmune encephalopathies from sporadic Creutzfeldt-Jakob disease. OBSERVATIONS In a clinical follow-up of an older man with rapidly evolving encephalopathy at a neuroscience center, unsuccessful treatment with immunosuppression based on the incorrect presumptive diagnosis of Morvan syndrome was followed by the correct histological diagnosis of sporadic Creutzfeldt-Jakob disease. CONCLUSIONS AND RELEVANCE Autoimmune encephalopathies raise important treatment options and potential for recovery. However, since neuronal antibodies may be positive in prion disease, interpretation can be complex and must be rooted in the clinical picture.

Convergence of afferents from superior sagittal sinus and tooth pulp on cells in the upper cervical spinal cord of the cat

Units in the dorsolateral area of the upper cervical cord respond to craniovascular stimulation. This study examined tooth pulp responses in this area in cats. Eleven of 21 units tested in the dorsolateral area had convergent inputs from superior sagittal sinus and tooth pulp; while 10 units had sagittal sinus, but not tooth pulp, input. Mean response latency to tooth pulp stimulation (25.8 ms) was significantly longer than to superior sagittal sinus stimulation (9.8 ms). Half of the units had cutaneous receptive fields; and in five units, action potentials could be evoked by electrical stimulation in the posterior complex of the thalamus.

Convergence of afferents from superior sagittal sinus and tooth pulp on cells in the thalamus of the cat.

We have previously shown convergence of craniovascular and tooth pulp afferents in the cervical spinal cord of cats. This study looked for similar convergence in the thalamus. Fifty-four thalamic cells with input from tooth pulp, superior sagittal sinus, or both, were identified. Twenty-nine cells with tooth pulp and superior sagittal sinus input were located in the ventrobasal complex or the intralaminar nuclei. Most of these 29 cells were also excited by cooling the contralateral tooth pulp, and 21 had receptive fields on the contralateral face or forelimb. Twenty cells excited by stimulation of superior sagittal sinus, and not tooth pulp, were found in several nuclei. The 5 cells excited by stimulation of tooth pulp, but not sagittal sinus, were restricted to the ventrobasal complex. The data confirm convergence from sagittal sinus, tooth pulp, and skin in the thalamus of anaesthetized cats.

Craniovascular nociceptive pathways relay in the upper cervical spinal cord in the cat

Units in the dorsolateral area of the upper cervical cord and the ventroposteromedial nucleus of the thalamus respond to stimulation of cranial vessels. To study the physiological role of the upper cervical cord in craniovascular transmission, we used a cryoprobe to interrupt reversibly neural transmission through the cord while recording in the thalamus. Twenty-one of 47 thalamic units tested showed reversible diminution in their response to superior sagittal sinus stimulation during cervical cord cooling. In contrast, receptive field responses and spontaneous thalamic activity were unaffected. These data suggest offt the cervical cord relays craniovascular nociceptive afferents.

A pilot study of the epilepsy risk awareness checklist (ERAC) in people with epilepsy and learning disabilities

PURPOSE People with epilepsy are at risk of injury, and protection from potential dangers must be balanced against the need for autonomy. We developed an epilepsy risk awareness checklist (ERAC) as a tool to assess potential risks of epilepsy and related injuries, aiming to improve management strategies. It was designed for use by specialist nurses (in learning disability and epilepsy), as there was no existing tool for this. This study refined and tested this checklist in patients with epilepsy and learning disability in a range of community settings. METHOD We used quantitative and qualitative measures to devise and revise the tool. Eleven qualified learning disability nurses completed the ERAC in three patients each (33 patients) using a purposive sampling method. They provided quantitative and qualitative feedback through questionnaires and interviews, and an expert panel reviewed and commented on the checklist. RESULTS The checklist was revised through the evaluation process. All eleven nurses concluded that they would use the tool again. CONCLUSION The epilepsy risk awareness checklist (ERAC) provides a measure of risk, and this study suggests that it is a useful tool in the care of people with learning disability and epilepsy. A larger scale study is planned.

Network meta-analysis and the comparison of efficacy and tolerability of anti-epileptic drugs for treatment of refractory focal epilepsy

We read with interest the recent paper on network meta-analysis [1] in which efficacy and tolerability of selected anti-epileptic drugs in people with refractory focal epilepsy were compared. Whilst network meta-analysis may be a powerful tool, the validity of the results must depend on the selection of studies included. In this respect, we are curious about several methodological points. The authors include some studies but not others that are of the same nature. The authors deem as appropriate doses those that most experienced epilepsy clinicians would consider unusual and the results that emerge would be considered misleading by most experienced epilepsy clinicians. Only one of the four drugs the authors suggest have efficacy and tolerability in focal epilepsies would be accepted as such by experienced epilepsy clinicians. Their recommendation of vigabatrin in this category is most surprising, given the significant adverse effects associated with its use. The paper illustrates the importance of ensuring that the results of any complex statistical process should always be checked against actual clinical experience. The authors selected for comparison only people receiving doses of the target drugs which they deemed appropriate. Despite the authors’ claim that they chose the selected doses based on their clinical experience, the choice seems arbitrary, is out of keeping with clinical experience and is not based on any stated evidence. For instance, only someone with little clinical experience of oxcarbazepine would consider doses over 1800 mg day−1 as appropriate. The dose of 2400 mg is poorly tolerated by most people. It is also unlikely that many people would tolerate doses of topiramate over 300 mg day−1. Several relevant studies were not included, without clear explanation. For instance, a key lacosamide study [2] was not included. The same apply for studies with topiramate [3] and levetiracetam [4]. Two relevant lamotrigine studies [5, 6] were also excluded. One could suggest that these were excluded as they were crossover studies, but then other crossover studies were included, such as a levetiracetam study [7]. It is imperative that consistent criteria are applied for study selection if this type of analysis is to be meaningful. The authors conclude that in their mixed-treatment network meta-analysis, levetiracetam, vigabatrin, sodium valproate and gabapentin emerge as the anti-epileptic drugs with the best combination of short term efficacy and tolerability. As experienced epilepsy clinicians having seen many thousands of patients, we do not consider that valproate and gabapentin should be considered as first line anti-epileptic drugs for people with focal epilepsy, whilst any epilepsy clinician would know that the risk of visual field loss with vigabatrin is far too high to contemplate its regular use. The authors’ recommendation on valproate appears to emanate from one old study comparing vigabatrin with valproate, in which a small number of people with epilepsy not controlled by carbamazepine were given either valproate or vigabatrin [8]. It is not clear why better quality data [9] were omitted from the analysis. For these reasons, the conclusions cannot be considered particularly helpful. The need for answers to the questions the authors set out to address remains. One important thing to remember is that epilepsy, a symptom-complex, is not a single disease but a collection of many different conditions for which the current clinical trials paradigm is completely inappropriate [10, 11].

Migraine: mimics, borderlands and chameleons

Diagnostically, headache is the easy part of migraine. It is the surrounds of migraine—the aura, prodrome and postdrome—that can be most challenging, and confused with other pathologies. This article examines the definition and variants of migraine; alternative diagnoses for which migraine may be mistaken (mimics); conditions that lie between migraine and other diagnoses (borderlands) and the possible presentations of migraine posing as other conditions (chameleons). The focus is on adults, with only passing reference to children. Migraine is more often a chameleon than a mimic; and it is the careful history that usually makes the distinction. Given migraines prevalence of 10–15%, relatively uncommon features of migraine occur quite often, in comparison with frequent manifestations of less common diseases. Thus, even rare or under-recognised presentations of migraine come into the differential diagnosis of many presentations.