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Biomedical subjects

Manjit S Matharu

Publications and source records attributed to Manjit S Matharu.

17 recordsLinked to original sources

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA)--a prospective clinical study of SUNCT and SUNA.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic features (SUNA) are described, although SUNA is rarely reported. The phenotype of SUNCT and SUNA was characterized from a large series of patients (43 SUNCT, 9 SUNA). Three attack types were identified: stabs, groups of stabs and saw-tooth attacks. The mean duration of stabs was 58 s (1-600 s); stab groups, 396 s (10-1200 s); and saw-tooth, 1160 s (5-12 000s). The attack frequency was a mean of 59 attacks/day (2-600), and this depended largely on the type of attack. The pain was orbital, supraorbital or temporal in 38 (88%) SUNCT and 7 (78%) SUNA, and also occurred in the retro-orbital region, side, top, back of head, second and third trigeminal divisions, teeth, neck and ear. All SUNCT patients had conjunctival injection and tearing. Two SUNA patients had conjunctival injection, four had tearing, but none had both. Other cranial autonomic symptoms included nasal blockage, rhinorrhoea, eyelid oedema, facial sweating/flushing and ear flushing. Cutaneous stimuli triggered attacks in 74% of SUNCT but only in 22% of SUNA patients. The majority (95% SUNCT and 89% SUNA) had no refractory period between attacks. For SUNCT 58% and for SUNA 56% of patients were agitated with the attacks. We propose a new set of diagnostic criteria for these syndromes to better encompass the clinical presentations and which include a wider range of attack length, wider trigeminal pain distribution, cutaneous triggering and lack of refractory period.

Adult↗

Prophylaxis of venous thromboembolism during early inpatient rehabilitation after acquired brain injury: how guidelines change management.

PURPOSE: To establish guidelines for prophylaxis of venous thromboembolism (VTE) in younger adults undergoing early inpatient rehabilitation following acquired brain injury (ABI). METHOD: A two-phase (phase 1: retrospective; phase 2: prospective) observational study was carried out involving patients admitted to an inpatient neurological rehabilitation unit during a 40-month period. In phase 1, VTE prophylaxis was prescribed on an ad hoc basis. In phase 2, prophylaxis was considered in accordance with guidelines agreed locally. The prescribing behaviour in each phase of the study was compared using a VTE risk stratification tool based on expert opinion and a review of the literature. RESULTS: Data were obtained on 94 patients in phase 1 and 23 patients in phase 2. During phase 1, the prophylactic prescribing behaviour of the referring hospitals and our unit after admission were similar ( p = 0.13). In phase 2, our prescribing behaviour had changed compared with that of the referring hospitals, with a significant increase in the proportion of patients on appropriate treatment ( p = 0.01) and a decrease in the numbers under-treated ( p = 0.002). We were also significantly less likely to under-treat ( p = 0.005) and more likely to over-treat ( p = 0.004) after admission during phase 2 compared with phase 1, whilst practice was variable in patients at moderate risk. CONCLUSIONS: Guidelines modify behaviour. They must stratify risk, particularly to avoid inconsistencies in the management of patients at moderate risk. There is a need to establish national guidelines for VTE prophylaxis during early inpatient rehabilitation after ABI; these guidelines should include a risk stratification tool.

Adolescent↗

Posterior hypothalamic activation in paroxysmal hemicrania.

OBJECTIVE: Paroxysmal hemicrania (PH) is a severe, strictly unilateral headache that lasts 2 to 30 minutes, occurs more than five times daily, is associated with trigeminal autonomic symptoms, and is exquisitely responsive to indomethacin. The purpose of the study was to determine the brain structures active in PH. METHODS: Seven PH patients were studied using positron emission tomography (PET). Each patient was scanned in three states: (1) acute PH attack-off indomethacin; (2) pain-free-off indomethacin; and (3) pain-free after administration of intramuscular indomethacin 100 mg. The scan images were processed and analyzed using SPM99. RESULTS: The study showed no significant activations during state 1 compared with state 2, but there was relative activation of the pain neuromatrix in both states 1 and 2 compared with state 3. This suggests that there is persistent activation of the pain neuromatrix during acute PH attacks and during interictal pain-free states off indomethacin that is deactivated by the administration of indomethacin. In addition, the untreated PH state was associated with significant activation of the contralateral posterior hypothalamus and contralateral ventral midbrain, which extended over the red nucleus and the substantia nigra. INTERPRETATION: These activated subcortical structures may play a pivotal role in the pathophysiology of this syndrome.

Adult↗

Thunderclap headache.

Thunderclap headache (TCH) is head pain that begins suddenly and is severe at onset. TCH might be the first sign of subarachnoid haemorrhage, unruptured intracranial aneurysm, cerebral venous sinus thrombosis, cervical artery dissection, acute hypertensive crisis, spontaneous intracranial hypotension, ischaemic stroke, retroclival haematoma, pituitary apoplexy, third ventricle colloid cyst, and intracranial infection. Primary thunderclap headache is diagnosed when no underlying cause is discovered. Patients with TCH who have evidence of reversible, segmental, cerebral vasoconstriction of circle of Willis arteries and normal or near-normal results on cerebrospinal fluid assessment are thought to have reversible cerebral vasoconstriction syndrome. Herein, we discuss the differential diagnosis of TCH, diagnostic criteria for the primary disorder, and proper assessment of patients. We also offer pathophysiological considerations for primary TCH.

Acute Disease↗

An audit of first seizures presenting to an Accident and Emergency department.

OBJECTIVES: To investigate whether patients presenting after a first seizure to an Accident and Emergency (A&E) department were being managed according to consensus recommendations. DESIGN: Retrospective audit. SETTING: UK District General Hospital over 6 months. METHODOLOGY: Hand search of Accident and Emergency notes for diagnoses of "seizure", "fit", "epilepsy" and "epileptic fit", followed by scrutiny of hospital and General Practice (GP) medical notes. RESULTS: Eighty three percent of patients discharged from the A&E department with a letter to take to their general practitioners, but only 20% of those referred directly to the neurology clinic, were lost to follow-up. Of the patients seen as out-patients by a neurologist, the median waiting time to clinic was 22 weeks, 18 weeks longer than recommended. The average time to having an MRI scan and EEG performed were 12 and 15 weeks, respectively. Twenty percent of patients seen by a neurologist were not felt to need further investigation for epilepsy. CONCLUSIONS AND RECOMMENDATIONS: All patients presenting after a first seizure should be directly referred to a neurology clinic from the A&E department. The currently proposed target time to specialist review is unrealistic without significant resource improvements. The provision of diagnostic guidelines and telephone advice by the neurology team prior to discharge from A&E may avoid unnecessary investigation.

Brain Diseases↗

Pituitary volume and headache: size is not everything.

BACKGROUND: Pituitary tumors are commonly associated with disabling headache. The accepted mechanisms for headache are dural stretch and cavernous sinus invasion. OBJECTIVE: To determine if there is a relationship between pituitary tumor size and the report of headache. DESIGN: We prospectively studied 63 patients who were initially seen with pituitary tumors. Clinical headache scores, pituitary tumor volume, and the extent of cavernous sinus invasion were obtained for each patient. RESULTS: The prevalence of headache was 70%. There was no positive correlation the between clinical headache score and pituitary volume (r = -0.32, P =.01, Spearman rank correlation). There was also no association between cavernous sinus invasion and headache. There was a strong association between pituitary-associated headache and a family history of headache (chi(2) = 8.36, P =.004). CONCLUSIONS: These data suggest that a pituitary tumor-associated headache may not simply be a structural problem. Other factors such as family history of headache, and the endocrine activity of the tumor may be equally important determinants of headache. Elucidating these mechanisms will aid in the treatment of these patients and further our understanding of other headache syndromes.

Cavernous Sinus↗

Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study.

Current practical evidence-based acute treatments of cluster headache are limited to subcutaneous and intranasal formulations of sumatriptan, and oxygen. Two small randomized, double-blind trials suggested efficacy of somatostatin in cluster headache. We sought to determine whether octreotide, a somatostatin analog, is effective in the abortive treatment of acute cluster headache. Patients with episodic and chronic cluster headache, as defined by the International Headache Society, were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 24-hour break, using subcutaneous octreotide microg or matching placebo. The primary end point was the headache response defined as very severe, severe, or moderate pain becomes mild or nil, at 30 minutes. The primary end point was examined using a multilevel analysis approach. A total of 57 patients were recruited of whom 46 provided efficacy data on attacks treated with octreotide and 45 with placebo. The headache response rate with subcutaneous octreotide was 52%, whereas that with placebo was 36%. Modeling the treatment outcome as a binomial where response was determined by treatment, using the patient as the level 2 variable, and considering period effect, sex, and cluster headache type as other variables of interest, we found that the effect of subcutaneous octreotide 100 microg was significantly superior to placebo (p < 0.01). Subcutaneous octreotide 100 microg is effective in the acute treatment of cluster headache when compared with placebo. Nonvasconstrictor treatment of acute cluster headache is possible.

Adolescent↗

Posterior hypothalamic and brainstem activation in hemicrania continua.

OBJECTIVE: To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography. BACKGROUND: Hemicrania continua is a strictly unilateral, continuous headache of moderate intensity, with superimposed exacerbations of severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic headaches and migraine in which the hypothalamus and the brainstem, respectively, have been postulated to play central pathophysiologic roles. We hypothesized, based on the clinical phenotype, that hemicrania continua may involve activations in the hypothalamus, or dorsal rostral pons, or both. METHODS: Seven patients with hemicrania continua were studied in two sessions each. In one session, the patients were scanned during baseline pain and when rendered completely pain free after being administered indomethacin 100 mg intramuscularly. In the other session, the patients were scanned during baseline pain and when still in pain after being administered placebo intramuscularly. Seven age- and sex-matched nonheadache subjects acted as the control group. The scan images were processed and analyzed using SPM99. RESULTS: There was a significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious. CONCLUSIONS: This study demonstrated activations of various subcortical structures, in particular the posterior hypothalamus and the dorsal rostral pons. If posterior hypothalamic and brainstem activation are considered as markers of trigeminal autonomic headaches and migrainous syndromes, respectively, then the activation pattern demonstrated in hemicrania continua mirrors the clinical phenotype, with its overlap with trigeminal autonomic headaches and migraine.

Adult↗

Cluster headache: focus on emerging therapies.

Cluster headache is a strictly unilateral headache that occurs in association with cranial autonomic features. It is an excruciating syndrome and is probably one of the most painful conditions known to mankind with female patients describing each attack as being worse than childbirth. In most patients, it has a striking circannual and circadian periodicity. This disorder has a highly stereotyped clinical phenotype and responds to specific therapies, thereby underlying the importance of distinguishing it from other primary headache syndromes. In this review, the clinical manifestations, differential diagnosis, diagnostic workup and treatment options for this syndrome have been outlined.

Analgesics↗

Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study.

Electrical stimulation of primary sensory afferents is known to have an antinociceptive effect. Animal and functional imaging studies suggest a role for supraspinal structures in this response. Eight patients with chronic migraine (> or =15 days per month of attacks of migraine without aura), who had shown a marked beneficial response to implanted bilateral suboccipital stimulators, were studied. Stimulation evoked local paraesthesia, the presence of which was a criterion of pain relief. On stimulation, the headache began to improve instantaneously and was completely suppressed within 30 min. On switching off the stimulation, the headache recurred instantly and peaked within 20 min. PET scans were performed using regional cerebral blood flow (rCBF) as a marker of neuronal activity. Each patient was scanned in the following three states: (1) stimulator at optimum settings: patient pain-free but with paraesthesia; (2) stimulator off: patient in pain and no paraesthesia; (3) stimulator partially activated: patient with intermediate levels of pain and paraesthesia. All scans were processed and analysed using Statistical Parametric Mapping (SPM) 99. There were significant changes in rCBF in the dorsal rostral pons, anterior cingulate cortex (ACC) and cuneus, correlated to pain scores, and in the ACC and left pulvinar, correlated to stimulation-induced paraesthesia scores. The activation pattern in the dorsal rostral pons is highly suggestive of a role for this structure in the pathophysiology of chronic migraine. The localization and persistence of activity during stimulation is exactly consistent with a region activated in episodic migraine, and with the persistence of activation of that area after successful treatment. The dorsal rostral pons may be a locus of neuromodulation by suboccipital stimulation. In addition, suboccipital stimulation modulated activity in the left pulvinar.

Adult↗

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing syndrome: a review.

The clinical features of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome have been reviewed in 50 patients reported in the English language literature. SUNCT syndrome is a rare condition that predominates slightly in men. The mean age at onset is 50 years. It is characterized by strictly unilateral attacks centered on the orbital or periorbital regions, forehead, and temple. Generally, the pain is severe and neuralgic in character. The usual duration ranges from 5 to 250 seconds, although the reported range of duration is 2 seconds to 20 minutes. Ipsilateral conjunctival injection and lacrimation are present in most, but not all patients. Most patients are thought to have no refractory periods and this has probably been unreported in the past. Episodic and chronic forms of SUNCT exist. The attack frequency varies from less than one attack daily to more than 60 attacks per hour. The attacks are predominantly diurnal, although frequent nocturnal attacks can occur in some patients. A functional magnetic resonance imaging study in SUNCT syndrome has demonstrated ipsilateral hypothalamic activation. SUNCT was thought to be highly refractory to treatment. However, recent open-label trials of lamotrigine, gabapentin, topiramate, and intravenous lidocaine have produced beneficial therapeutic responses. These results offer the promise of better treatments for this syndrome, but require validation in controlled trials.

Conjunctival Diseases↗

Somatostatin infusion withdrawal: a study of patients with migraine, cluster headache and healthy volunteers.

Migraine and cluster headache are the most common disabling primary headache syndromes and are typically episodic. A reliable method of triggering such headache attacks facilitates the study and treatment of these disorders. There is sufficient clinical and laboratory evidence to suggest that somatostatin withdrawal may be a useful way of triggering headache. We studied 15 subjects, eight migraineurs, four cluster headache sufferers and three healthy controls. Each subject had a standard somatostatin infusion, 250 microg/h for 3.5h. Subjects were followed for 24h post-infusion. Growth hormone was suppressed in each subject demonstrating a biologically active infusion of somatostatin. None of the non-headache sufferers had pain. Seven of eight migraine sufferers had no immediate headache and no delayed headache. One migraineur experienced short lasting headache with no migrainous features. Three of four patients with cluster headache had no significant pain with the infusion, while one had pain after 1h. The results suggest that somatostatin infusion is not a reliable way to produce headache in experimental settings in either migraine or cluster headache. The data do not exclude a role for somatostatinergic mechanisms in primary headache.

Adult↗

Management of trigeminal autonomic cephalgias and hemicrania continua.

The trigeminal autonomic cephalgias (TACs) are a group of primary headache disorders characterised by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features. This group of headache disorders includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). Although hemicrania continua has previously been classified amongst the TACs, its nosological status remains unclear. Despite their similarities, these disorders differ in their clinical manifestations and response to therapy, thus underpinning the importance of recognising them. We have outlined the clinical manifestations, differential diagnoses, diagnostic workup and the treatment options for each of these syndromes.

Analgesics↗

Persistence of attacks of cluster headache after trigeminal nerve root section.

Cluster headache is a strictly unilateral headache that occurs in association with cranial autonomic features. We report a patient with a trigeminal nerve section who continued to have attacks. A 59-year-old man described a 14-year history of left-sided episodes of excruciating pain centred on the retro-orbital and orbital regions. These episodes lasted 1-4 h, recurring 2-3 times daily. The attacks were associated with ipsilateral ptosis, conjunctival injection, lacrimation, rhinorrhoea and facial flushing. From 1986 to 1988, he had trials of medications without any benefit. In February 1988, he had complete surgical section of the left trigeminal sensory root that shortened the attacks in length for 1 month without change in their frequency or character. In April 1988, he had further surgical exploration and the root was found to be completely excised; post-operatively, there was no change in the symptoms. From 1988 to 1999, he had a number of medications, including verapamil and indomethacin, all of which were ineffective. Prednisolone 30 mg orally daily rendered the patient completely pain free. Sumatriptan 100 mg orally and 6 mg subcutaneously aborted the attack after approximately 45 and 15 min, respectively. He was completely anaesthetic over the entire left trigeminal distribution. Left corneal reflex was absent. Motor function of the left trigeminal nerve was preserved. Neurological and physical examination was otherwise normal. MRI scan showed a marked reduction in the calibre of the left trigeminal nerve from the nerve root exit zone in the pons to Meckel's cave. An ECG-gated three-dimensional multislab MRI inflow angiogram was performed. No dilatation was observed in the left internal carotid artery during the cluster attack. Blink reflexes were elicited with a standard electrode and stimulus. Stimulation of the left supraorbital nerve produced neither ipsilateral nor contralateral blink reflex response. Stimulation of the right supraorbital nerve produced an ipsilateral response with a mean R2 onset latency of 36 ms and a contralateral response with a mean R2 onset latency of 32 ms. Lack of ipsilateral vessel dilatation makes the role of vascular factors in the initiation of cluster attacks questionable. With complete section of the left trigeminal sensory root the brain would perceive neither vasodilatation nor a peripheral neural inflammatory process; however, the patient continued to have an excellent response to sumatriptan. The case illustrates that cluster headache may be generated primarily from within the brain, and that triptans may have anti-headache effects through an entirely central mechanism.

Blinking↗