Dr Manjit Matharu MRCP, PhD
The Headache Group conducts clinical and laboratory-based research into the mechanisms and management of headache syndromes.
The Headache Group has performed seminal functional imaging studies in primary headaches. Functional imaging studies had previously demonstrated specific activation of the brainstem in episodic migraine and the posterior hypothalamus in cluster headache (CH). The group helped further refine the localisation of the brainstem activation in episodic and chronic migraine to the dorsal rostral pons using positron emission tomography (PET) and demonstrated that lateralisation of pain in migraine is due to lateralised brain dysfunction. The group have studied cerebral activation patterns in paroxysmal hemicrania (PH) and short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), which along with CH are grouped together as trigeminal autonomic cephalalgias. Significant activation of the posterior hypothalamus and ventral midbrain region was demonstrated in PH using PET while posterior hypothalamic activation was demonstrated in SUNCT using functional magnetic resonance imaging. In a PET study in hemicrania continua (HC), the clinical phenotype of which overlaps with migraine and the trigeminal autonomic cephalalgias, significant activation of the posterior hypothalamus, dorsal rostral pons and ventrolateral midbrain was demonstrated. These series of studies suggested that primary headache may be pathophysiologically differentiated on the basis of distinct patterns of brain activation, with hypothalamic and dorsal pontine activation as markers of trigeminal autonomic cephalalgias and migrainous syndromes, respectively. These studies draw attention to the structures that may play a pivotal role in the pathophysiology of primary headaches.
The classification and clinical spectrum of headache disorders have hitherto been poorly defined though large strides have been made in this area over the last two decades. The Headache Group has accumulated relatively large cohorts of various headaches syndromes and systematically studied their clinical phenotypes. This has led to the further refinement of the clinical spectrum of SUNCT, short-lasting unilateral neuralgiform headache with cranial autonomic symptoms (SUNA), PH and headaches in patients with pituitary disorders.
Headache is a significant problem in patients with pituitary tumours. Dural stretch and cavernous sinus invasion were widely considered to be the mechanism of headache in pituitary disease. The Headache Group has studied a large cohort of patients with pituitary disease. The clinical characteristics of headache and the pituitary structure, including the tumour volume and extent of cavernous sinus invasion, were carefully studied. We demonstrated that there was no association between headache and pituitary structure, but there was a strong association of headache with the endocrine activity of the tumour and patients’ prior predisposition to headache. We established that headache in patients with pituitary disorders is predominantly governed by neurohumoral rather than structural factors.
The Headache Group has advanced therapeutics by conducting controlled drug trials in various headache syndromes and describing neurostimulation in medically intractable headache syndromes. While studying patients with pituitary tumours, it was observed that octreotide, which was prescribed for endocrine indications, was effective for the treatment of headaches. This raised the possibility that this agent may be effective in primary headache syndromes. We conducted randomised controlled trials of octreotide in CH and migraine. These proof-of-principle studies established that octreotide is effective in CH but not migraine. The nominee also provided the first case descriptions of the efficacy of open-label use of topiramate in HC and SUNCT. This subsequently led to a controlled trial of topiramate in SUNCT (submitted for publication). The nominee provided the first description of the efficacy of occipital nerve stimulation (ONS) in eight patients with medically refractory chronic migraine. In addition, the nominee studied the mechanism of action of ONS using PET and described the central pain-modulating circuits that are activated in these patients during neurostimulation.
Dr Manjit Matharu, Senior Lecturer and Honorary Consultant Neurologist
Clinical Research Fellows
Dr Giorgio Lambru
Dr Surat Tanprawate
Dr Paul Shanahan, Consultant Neurologist, The National Hospital for Neurology and Neurosurgery
Dr Declan Chard, Consultanat Neurologist, The Institute of Neurology and The National Hospital for Neurology and Neurosurgery
Dr Timothy Young, Locum Consultant Neurologist, The National Hospital for Neurology and Neurosurgery and Whittington Hospital
Mr Laurence Watkins, Consultant Neurosurgeon, The National Hospital for Neurology and Neurosurgery
Mr Ludvic Zrinzo, Consultant Neurosurgeon, The National Hospital for Neurology and Neurosurgery
Prof Marwan Hariz, Consultant Neurosurgeon, The National Hospital for Neurology and Neurosurgery
Prof Marwan Jahanshahi, Clinical Neuropyschologist, The Institute of Neurology and The National Hospital for Neurology and Neurosurgery
Functional neuroimaging studies in primary headache syndromes have strongly implicated a central role for the posterior hypothalamic and dorsal pontine activation as markers of cranial autonomic features and migrainous symptoms, respectively. Structural neuroimaging techniques are also starting to provide an insight into the pathophysiology of primary headaches. Voxel-based morphometry, an automated whole brain technique that is sensitive to subtle macroscopic and mesoscopic structural differences between groups of subjects, has been used to demonstrate hypothalamic abnormality in cluster headache. This technique are being utilised to determine whether there are structural abnormalities in other primary headaches.
The clinical group attracts tertiary level referrals, which is facilitating the accumulation of large cohorts of relatively rare headache syndromes. The clinical phenotypes of these syndromes are being carefully defined. The current focus is on further defining the trigeminal neuralgiform disorders including short-lasting unilateral neuralgiform headache attacks with conjunctival injevtion and tearing (SUNCT), short-lasting unilateral neuralgiform disorders with autonomic symproms (SUNA) and trigeminal neuralgia.
The Headache Group was involved in pioneering the use of occipital nerve stimulation and deep brain stimulation in intractable headaches. The long-term follow up of these patients will be described and mechanism of action of these neuromodulation techniques will be studied further with functional neuroimaging techniques.
MSc Clinical Neuroscience Course
Headache courses at Royal College of Physicians (London)
Medical student teaching
Dr Manjit Matharu
Senior Lecturer and Honorary Consultant in Neurology
Institute of Neurology
London WC1N 3BG
Academic secretary: Olga Shapeero
Tel: +44 (0)20 7829 8749
Fax: +44 (0)7092 120797
NHS Secretary: Clare Lipscombe
Tel: +44 (0)8451 555000 ext: 723664
Fax: +44 (0)207 829 8784
Private Secretary: Sarah Mazdon
Tel: +44 (0)7595900535
Fax: +44 (0)7092 120797