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  1. 1. Diagnosis of focal headache Review Headache with focal neurological signs or symptoms: a complicated differential diagnosis Jean Schoenen and Peter S Sándor Headache syndromes can be associated with focal Panel 1. Summary of the disorders described in this neurological symptoms or signs. Good knowledge of review and their classification in the International primary headaches, a detailed history and a thorough clinical Classification of Headache Disorders1 examination are prerequisites for their differential diagnosis. The neurological symptoms produced by the migraine aura Migraine with aura (code 1.2) and ophthalmoplegic migraine (code 13.17) are the most characteristic and recognisable. However, Cluster headache and other trigeminal-autonomic cephalgias (code 3) structural lesions, such as vascular malformations, can Ischaemic stroke and transient ischaemic attacks (code 6.1) produce similar symptoms to migraine with aura, which Intracerebral haemorrhage (code 6.2.1) highlights that paraclinical investigations are necessary in Subarachnoid hemorrhage (code 6.2.2) most patients with headache and focal neurological Unruptured vascular malformations (code 6.3) symptoms. In this review, we provide an overview of the Arteritis (code 6.4) differential diagnosis of the most common headache Carotid or vertebral artery pain (code 6.5) disorders with focal neurological symptoms or signs to Cerebral venous thrombosis (code 6.6) refresh the practising neurologist’s differential diagnostic High cerebrospinal fluid pressure (code 7.1) knowledge for the clinical situation and to aid the teaching of Low cerebrospinal fluid pressure (code 7.2) neurology residents. Intracranial neoplasm (code 7.4) Syndrome of transient headache and neurologic deficits with Lancet Neurol 2004; 3: 237–45 cerebrospinal fluid lymphocytosis (“HaNDL”, code 7.8) Trigeminal neuralgia (tic douloureux; code 13.2) Tolosa-Hunt syndrome (code 13.16) Headache is a symptom with various causes. In some Acute herpes zoster (code 13.15.1) & post-herpetic neuralgia (code disorders, headache is associated with focal neurological 13.15.2) signs or symptoms. If this happens, one has to distinguish between a primary headache (eg, migraine) and a symptomatic headache secondary to an underlying caused by a structural lesion if symptoms appear during and infectious, inflammatory, vascular, neoplastic, or epileptic after the headache, or if they outlast it. The rare exception to disorder. This differential diagnosis may be difficult in some the latter is hemiplegic migraine. patients. Above all, its prerequisite is a precise knowledge of After migraine with aura, the most common headache the clinical spectrum and characteristics of primary disorders associated with focal neurological signs (in this headache disorders. Any clinical presentation that deviates case, ipsilateral autonomic signs) are cluster headache and even slightly from the classical features of primary headaches the related trigeminal autonomic cephalalgias. warrants a thorough work-up in order to search for a secondary cause of headache. We will focus on the most Migraine common disorders that cause headache and focal Migraine is a multifaceted disorder, of which the head pain neurological symptoms or signs (panel 1). In this review, we is only one component. It is a primary CNS disorder, but in refer to the latest edition of the Classification and Diagnostic some instances it may occur for the first time in close Criteria for Headache Disorders, Cranial Neuralgias and temporal relation to a secondary headache. Migraine is a Facial Pain. Our goal is to refresh the practising paroxysmal disorder characterised by attacks, which are neurologist’s differential diagnostic knowledge for the separated by symptom-free intervals. Similar to epilepsy, clinical situation and to aid the teaching of neurology migraine is characterised by the repetition of attacks rather residents. The following general rules of thumb (figure 1) are useful when confronted with a headache syndrome in the clinical situation. Long-lasting headaches (eg, over weeks or JS is at the Departments of Neurology & Neuroanatomy, Headache months) associated with neurological abnormalities are Research Unit, University of Liège, Belgium; PSS is at the Neurology Department, Headache & Pain Unit, University Hospital typically caused by structural brain lesions. If headaches are Zürich, Switzerland. episodic in nature, neurological signs or symptoms may Correspondence: Prof Jean Schoenen, University Department of precede or accompany and outlast the headache. The Neurology, CHR Citadelle, Boulevard du XIIème de Ligne, disorder is likely to be benign (ie, not secondary) if the 1-B-4000, Liège, Belgium. Tel +32 4 225 6451; fax +32 4 225 6451; symptoms occur before the headache; and it is likely to be email THE LANCET Neurology Vol 3 April 2004 237 For personal use. Only reproduce with permission The Lancet Publishing Group.
  2. 2. Review Diagnosis of focal headache duration.3 The headache that follows the aura may phenotypically resemble Headache with focal neurological signs or symptoms tension-type headache (code 2) and recently migrainous-like auras Episodic headache Long-lasting headache (hours or days) (weeks or months) preceding typical cluster-headache attacks were described in rare patients.5 Headache may even be completely absent (code 1.2.3). Many patients have attacks of migraine both Neurological signs Neurological signs or symptoms with and without aura. In the so-called or symptoms accompany or outlast the headache precede the headache early-morning migraine, when patients wake up with migrainous Symptomatic headache headache, it is impossible to ascertain Primary headache (suspect structural lesion) whether the attack was preceded by an aura or not, although some patients Figure 1. Identification of the cause of headache. report dreaming and aura. Basilar type migraine (code 1.2.6) than a single attack, which may recur in many individuals is a controversial entity, which is described as migraine with under certain circumstances (eg, stress). aura where symptoms can be attributed to dysfunction in In the absence of a biological marker, the diagnosis is the brainstem or in both hemispheres and where no motor entirely based on clinical characteristics. Migraine without weakness is present. In addition to a fully reversible visual, aura (code 1.1) is not associated with neurological sensory, or speech aura without motor weakness, two or symptoms or signs. In migraine with aura (1.2) the headache more aura symptoms have to be of the following type: phase is typically preceded by focal neurological symptoms dysarthria, vertigo, tinnitus, decreased hearing, double (case report 1). vision, ataxia, decreased level of consciousness, simultaneous bilateral visual symptoms in both the temporal and nasal field of both eyes, and simultaneous Case report 1 bilateral paraesthesias. The differential diagnosis of such This 25-year-old woman visits her doctor because of disabling migraine phenomena include vascular and other pathologies, the attacks since the age of 20 years. Each attack starts with visual disturbances: a small spot in one hemifield first becomes fuzzy, then it enlarges over a few minutes interfering with (for example) reading. The greyish visual field defect is surrounded by “worm-like” white luminous strings and occupies the whole hemifield after about 10 min (to the right in some attacks, to the left in others). Then, about a third of the way through the attacks she feels tingling and numbness in the hand on the side of the visual field defect; this may “jump” to the ipsilateral labial commissure and rarely spread over the whole arm. These neurological symptoms disappear gradually after 20–30 min and are replaced by a hemicrania—typically located on the side opposite to the field defect. The headache is of moderate intensity, associated with anorexia and mild sensitivity to light; if untreated, it lasts for 4–6 h. Attacks occur irregularly (average of six to eight per year) and tend to cluster on successive days in the same week. The patient does not report any trigger factors. Given the typical pattern of the symptoms, there is no indication for further investigation. Migraine with aura (1.2) Visual disturbances are the most common aura symptoms, occurring in about 99% of patients.2 Sensory symptoms and Figure 2. BOLD (blood-oxygen level dependent) activity changes from a motor or speech disturbances seldom occur without pre- region of interest in the visual cortex, acquired before and during existing visual symptoms.3 episodes of induced visual aura. Top: Anatomical images in “inflated” Migrainous aura phenomena are thought to be caused by cortical hemispheres showing the medial view (similar to a conventional midsagittal view). Images were sampled after intervals of 32 s, showing spreading depression3 (figure 2)4 and can be distinguished the same region of interest (circles) in V1. Bottom: Changes in MR signal from those produced by a seizure or by a transient ischaemic over time from the circled region of interest. Variations in time are colour- attack (TIA) by their progressive onset, their spreading over coded (deep red to magenta). Before the onset of the aura, the BOLD time, and their quality (table). In patient care this distinction response to intermittent visual stimulation shows a normal, oscillating is a common problem and clinicians commonly rely on activation pattern. After the onset of aura, the BOLD response showed an increase in mean level ( ), a substantial suppression to light modulation phenomenology, when making their diagnosis. ( ), followed by partial recovery of the response to light modulation at Compared with migraine without aura, migraine with decreased mean ( ). Reproduced from the Proceedings of the National aura is characterised by headache of low intensity and short Academy of Sciences USA.4 238 THE LANCET Neurology Vol 3 April 2004 For personal use. Only reproduce with permission The Lancet Publishing Group.
  3. 3. Diagnosis of focal headache Review Differential diagnosis of focal paroxysmal neurological symptoms Feature TIA Epilepsy Migraine Onset Sudden Sudden Progressive Progression rate None Fast Slow Different symptoms Simultaneous In succession In succession Type of visual symptoms Negative Positive coloured Negative or positive, uncoloured Territory Vascular Cortical Cortical Duration Short (10–15 min) Short (min) Long (30–60 min) possibility of which should be taken seriously—therefore Cluster headache and other trigeminal- the threshold for diagnosing basilar type migraine should be autonomic cephalgias high and preceded by high-quality cerebral imaging. The most typical feature of cluster headache is the temporal Hemiplegic migraine may occur in familial6 (code 1.2.4) clustering of attacks during several weeks separated by or sporadic7 (code 1.2.5) forms. This rare subtype of remissions of at least 14 days, but generally of several months migraine is characterised by the occurrence of hemiparesis (episodic cluster headache, code 3.1.1.). In chronic cluster or hemiplegia, with a varying duration from 5 min to headache (code 3.1.2) remissions of at least 1 month are several days, during the aura phase. In the familial disorder, absent for more than 1 year. the transmission is autosomal dominant and, in general, Cluster headache is a primary neurovascular headache onset is before age 20 years. In some families the migraine that is unilateral but differs from migraine. Characteristics may be associated with cerebellar ataxia, epilepsy, or distinguishing cluster headache from migraine are short susceptibility to coma after minor head trauma. Familial duration (typically 30–45 min), presence of autonomic hemiplegic migraine has attracted much interest because of symptoms on the painful side, and the extreme intensity of the finding of mutations in a chromosome 19p13 gene the pain. Most patients are agitated and pace the floor, which (which codes the 1 subunit of a voltage dependent P/Q is clearly different from people with migraine who generally calcium channel) in most patients with the familial lie down and seek rest during the attack.14 Cluster headache disorder8 and in the ATP1A2 gene on chromosome 1q23 attacks generally happen in the evening or during sleep. (which codes the 2 subunit of the Na+/K+ pump) in some Cluster headache has to be distinguished from trigeminal families.9 Diagnosis of hemiplegic migraine, especially the neuralgia. In the International Headache Society’s sporadic form, will require neuroimaging as well as a classification, the trigeminal autonomic cephalalgias lumbar puncture to rule out pseudomigraine with (TACs)15 are grouped with cluster headache. They share the temporary neurological symptoms and lymphocytic clinical hallmark of unilateral headache with prominent pleocytosis10 (code 7.8). ipsilateral cranial parasympathetic autonomic features. Cluster headache is a rare disorder with prevalence below Complications of diagnosis 0·1%;16 about 10% of patients have the chronic form.17 The Persistent aura without infarction (1.5.3) and migrainous onset of the first attack is typically between 20 years and infarction (code 1.5.4) complicate the diagnosis of migraine 40 years of age; about 70% of patients are men18 and, for with aura. In the former, one or more aura symptoms unknown reasons, there is an association with smoking. persist for more than 24 h and it is important to exclude Genetic influences seem to be less pronounced than in migrainous infarction by MRI including diffusion-weighted migraine, but familial disorder with an autosomal dominant imaging. Migrainous infarction is characterised by inheritance pattern does exist.19 Recent studies suggest an neurological deficit during a migraine attack that is typical involvement of the posterior ventral hypothalamic grey of those previously experienced by a patient; the defecit matter in the generation of attacks,20 although the cavernous must last for more than 60 min and be associated with an sinus may play a part during the attack itself.21 Cluster-like ischaemic infarction in the relevant area as shown by headaches, as well as other TACs, can be caused by organic neuroimaging techniques. Most importantly, other causes lesions—the most common of which are pituitary of infarction have to be ruled out.11 adenomas.22 Ophthalmoplegic “migraine” (code 13.17) is a very rare Other headaches classified in the group of the TACs, disorder that typically starts in childhood. It is characterised episodic paroxysmal hemicrania (code 3.2.1), and chronic by repeated attacks of headache with migrainous features, paroxysmal hemicrania (code 3.2.2) differ from cluster but with typically long duration of a week or more, headache by a shorter duration, a higher frequency of associated with a palsy of one or more of the cranial nerves attacks, and a greater prevalence in women than in men.15 involved in eye movements. Intracranial mass lesions have to The so called SUNCT (short-lasting unilateral neuralgiform be excluded for its diagnosis. Several MRI studies have headache with conjunctival injection and tearing) syndrome shown reversible thickening or contrast enhancement of the (code 3.3) is characterised by the shortest attack duration cisternal portion of the oculomotor nerve.12 This finding (10–200 s) and pronounced autonomic signs. If such a suggests that the disorder is caused by an inflammatory syndrome is suspected, a lesion in the posterior fossa must oculomotor neuropathy13 and that “ophthalmoplegic be ruled out, as this might mimic the primary form.23–26 migraine” is a misnomer. Hemicrania continua (code 3.4) is a non-remitting form of THE LANCET Neurology Vol 3 April 2004 239 For personal use. Only reproduce with permission The Lancet Publishing Group.
  4. 4. Review Diagnosis of focal headache TAC. It shares with paroxysmal hemicrania an absolute occipital headache associated with neck stiffness may responsiveness to indometacin,27 which is part of their indicate the onset of cerebellar pressure coning caused by a diagnostic criteria. supratentorial subdural haematoma. Headache associated with vascular disorders Subarachnoid haemorrhage (code 6.2.2) All headaches in this group have symptoms or signs of a Headache caused by subarachnoid haemorrhage (SAH) is vascular disorder, appear as a new symptom or as part of a typically abrupt in onset (split-second headache)—which is its clinical picture previously unknown in the patient, and are key feature—and incapacitating in severity. When not in close temporal relation to the onset of the vascular maximum from the beginning, time from onset to greatest disorder. pain intensity is less than 60 min for ruptured aneurysm and less than 12 h if caused by an arteriovenous malformation. Acute ischaemic cerebrovascular disease (code 6.1) The headache is diffuse and commonly occipital radiating to The importance of headache as a symptom of ischaemic the neck. It can be accompanied by blunting of consciousness, cerebrovascular disease is still neglected by many physicians. vomiting, and stiff neck. CT scan (which may be normal in However, comprehensive reviews have shown several 10% of patients) and CSF examination can confirm the associations.28,29 1) The incidence of headache accompanying diagnosis of subarachnoid haemorrhage (case report 2).36 transient ischaemic attacks (TIAs) or strokes varies from 15–65% between studies (average 30%). Headache seems to Case report 2 be more likely in patients with posterior circulation A 50 year-old woman suddenly presented with a posterior headache that ischaemia. 2) Headache precedes the event in about 10% of was rapidly followed by a scintillating scotoma in her left visual hemifield patients with haemorrhage or ischaemic attack. 3) The and paraesthesias of the left hand. Neurological symptoms lasted for headache is typically on the side of the affected artery or 45 min, but the headache remained intense for several hours and was frontal when the carotid or the posterior cerebral arteries are accompanied by nausea and vomiting. The patient has no personal or family history of migraine. A CT scan shows blood in the subarachnoid involved. In basilar or vertebral artery stenosis or occlusion space in the parieto-occipital regions predominantly on the right side the headache is typically occipital and bilateral. 4) In (figure 3). ischaemic cerebrovascular disease, headaches vary between continuous and throbbing, and most are of moderate intensity. 5) Headache at the onset of the ischaemic stroke Unruptured vascular malformation (code 6.3) does not help to distinguish embolic from atherothrombotic About 25% of patients with an intracranial aneurysm report stroke. Headache is probably less common in lacunar unusual headaches before a rupture occurs, partly of a infarction. “thunderclap” type. These are generally called “sentinel” or Whether or not migraine is an independent risk factor for ischaemic stroke is still debated. Several surveys indicate that this is only true in young women with migraine with aura, and that in these patients the risk is amplified by use of the contraceptive pill and by smoking.11,30-34 Non-traumatic and traumatic intracranial haemorrhage As a diagnostic element, headache is far more useful in haemorrhagic than in ischaemic stroke, because it is more commonly the presenting symptom. The overall incidence of headache as a major symptom of intracerebral haemorrhages (code 6.2.1) ranges from 36–66%.28 In all the published series there is a proportion of non-comatose, non- aphasic patients who do not have headaches—ranging from 10% in the basal ganglia to 30% in lobar haemorrhages. In patients with head trauma, who recover consciousness and subsequently deteriorate, headache is a common and useful indicator of the late development of an acute epidural (code 5.5.1) or a subdural (code 5.5.2) haematoma. This type of headache may be similar to that caused by high intracranial pressure. Subdural haematomas can sometimes produce a characteristic paroxysmal type of headache that comes and goes irregularly throughout the day, lasts only a couple of minutes, and is generally accompanied by sympathetic overactivity.35 Most are frontal, but when the subdural haematoma is in the posterior fossa, the headache Figure 3. CT scan (horizontal section) showing a subarachnoid is likely to be occipital. In the post-traumatic situation, haemorrhage over the right parietal cortex. 240 THE LANCET Neurology Vol 3 April 2004 For personal use. Only reproduce with permission The Lancet Publishing Group.
  5. 5. Diagnosis of focal headache Review “premonitory” headaches37 and are thought to be caused by Arteritis (code 6.4) the aneurysm intermittently leaking.28 Not every severe Giant-cell arteritis (temporal arteritis or Horton’s disease; headache of abrupt onset is a symptom of an intracranial code 6.4.1) is any type of new persisting headache and one or aneurysm (code 6.3.1). Most patients struck by thunderclap more of the following: swollen and tender scalp arteries with headache, who have normal CT scan and lumbar puncture high erythrocyte sedimentation rate or C-reactive protein; a results, do not subsequently present with subarachnoid close temporal relation with possible other symptoms and haemorrhage.38,39 There is no reliable difference in the clinical signs of giant-cell arteritis; and major improvement or phenotype between “primary thunderclap headache” (code disappearance of headache within 3 days of steroid therapy. 4.6) and the headache caused by subarachnoid The presence of typical histopathological features on haemorrhage40,41 (code 6.2.2). temporal artery biopsy is no longer a mandatory diagnostic Consequently, the following guidelines are helpful in requirement. patients with an abrupt “worst headache of my life”, and a Typical focal neurological complications are claudication normal neurological examination: first take a CT scan; if of jaw muscles and visual loss due to ischaemia of the optic normal, do a lumbar puncture. If the lumbar puncture is nerve and retina. The frequency of visual loss has been normal, the patient can be reassured that the headache is variously reported to be between 7% and 60%.46 Visual benign (but it may recur in some patients). If any feature of disturbances require immediate and intense treatment with the CT scan or lumbar puncture is abnormal, a conventional steroids, because the prognosis for recovery of vision lost for angiography is required. The role of magnetic resonance more than a few hours is poor. Stroke with involvement of angiography is not yet established. cerebral arteries may occur. Arteriovenous malformations (code 6.3.2), which account for 6% of all subarachnoid haemorrhages,28 commonly cause Carotid or vertebral artery pain (code 6.5) focal seizures or neurological deficits. Although the relation of Ipsilateral headache or cervical pain may be the only migraine and other headaches to unruptured arteriovenous manifestation of carotid or vertebral dissection (code malformations is poorly studied, there are several case reports 6.5.1), or it can accompany focal neurological symptoms of them mimicking attacks of migraine with aura.42–44 Possible (case report 4). This is of particular importance, as diagnostic clues are strictly unilateral symptom localisation, a generally, the headaches occur early and precede lack of family history for migraine, absence of visual aura ischaemia, the most feared complication of a dissection.47 symptoms, and atypical auras (case report 3). Most headaches are ipsilateral to the dissected artery and severe. Case report 3 A 40-year-old man had headache attacks since age 17 years. Attacks Case report 4 started with scintillations in his left visual field accompanied by While horse riding, a 26-year-old woman suddenly felt right nuchal pain paraesthesias and numbness of the entire left side of the body. These of moderate intensity. 2 h later she had a visual disturbance that she neurological symptoms were lock-sided and followed after a few minutes described as a general decrease in visual acuity accompanied by diffuse by a right hemicrania of moderate intensity. Headaches lasted several scintillations. Visual symptoms lasted for 15 min and were followed by a hours, the sensory symptoms outlasted the headaches by 1–2 h. The left non-throbbing hemicrania associated with mild photophobia, frequency of attacks varied over the years by two to ten a year and there phonophobia, and osmophobia. She lay down and fell asleep, and on was no family history of migraine. He was diagnosed as having migraine awakening all symptoms had disappeared. She had no personal or with visual aura. Neuroimaging disclosed a right parieto-occipital family history of migraine. An angiography showed a dissection of the left angioma (figure 4) that was surgically treated. The patient has not vertebral artery between cervical segments C4 and C2. Cutaneous reported any attack since. biopsy was characteristic of Ehlers-Danlos syndrome type 2. Cerebral venous thrombosis (code 6.6) Headache is the most common, and typically first, symptom in cerebral venous thrombosis. It is generally diffuse and subacute. Its intensity is highly variable. Associated neurological signs (focal deficit or seizures), or raised intracranial pressure, are present in most patients. Headache can occasionally be the only symptom of cerebral venous thrombosis,48 which is another reason why persistent new-onset headache should prompt appropriate investigations. Headache attributed to nonvascular intracranial disorder Within this group of headaches, we will focus on the more common disorders, the diagnosis of which is difficult at a Figure 4. Angiographic demonstration of a parieto-occipital arteriovenous stage when headache is the only symptom such as in benign malformation mimicking migraine with aura. Reproduced with permission intracranial hypertension, post-lumbar puncture headache, from the American Medical Association.45 and headache associated with brain tumour. THE LANCET Neurology Vol 3 April 2004 241 For personal use. Only reproduce with permission The Lancet Publishing Group.
  6. 6. Review Diagnosis of focal headache High CSF pressure (code 7.1) Idiopathic intracranial hypertension (code 7.1.1), also called pseudotumour cerebri or benign intracranial hypertension, may mimic chronic tension-type headache: it is generalised, non-throbbing, and sometimes of low or moderate intensity. It is increased by coughing or straining. The following symptoms are characteristic for the diagnosis of idiopathic intracranial hypertension:49 predominance in young, obese women (93%); most severe headache ever experienced by the patient (93%); nausea (57%); vomiting (30%); orbital pain (43%); transient visual obscuration (71%); diplopia (38%); and visual loss (31%). Papilloedema, without neuroradiological abnormalities (except for possible “empty sella”), is pathognomonic for this disorder.50 CSF cytology is normal, but protein content may be low. Axial CT may show narrow, slit-like ventricles. Low CSF pressure (code 7.2) The clinical hallmark of low CSF pressure headache is that Figure 5. Patchy pachymeningeal contrast enhancement in a patient with the pain is aggravated by orthostasis and disappears in a orthostatic headache caused by intracranial hypotension resulting from a supine position. The time lag after change of position can be dural leak after epidural anaesthesia. up to 15 min. The headache may be frontal, occipital, or diffuse and is typically severe, dull, or throbbing. Other relieve many of these headaches. If there is variation during symptoms include nausea, vertigo, and tinnitus, and the 24 h cycle, the headache is typically worse in the early shaking of the head aggravates pain. Results of physical morning hours. This variation is more prominent with examination are generally normal. Sixth-nerve palsy may rapidly growing tumours than with those of slower growth. occur and is reversible in most patients. Normal spinal fluid In 30–80% of patients the headache overlies the pressure ranges from 0–30 mm H2O in the lateral supine projection of the tumour to the nearest skull surface. Some position.51,52 general rules about headache as an aid to tumour- The most common cause of low CSF pressure is lumbar localisation in patients with brain tumour have been puncture51 (case report 5). According to a recent study, the proposed by Dalessio.56 1) In about a third of all patients, incidence of headache after lumbar puncture (code 7.2.1) headache overlies the tumour. 2) If the tumour is above the may reach 37%.53 Headache after lumbar puncture is more tentorium, the pain is commonly at the vertex or in the common in patients with a history of primary headaches.51 frontal region. 3) If the tumour is below the tentorium, the There are many other causes of low-pressure-headache pain is occipital and cervical muscle spasms may be present. syndrome—such as post-traumatic, postoperative, or 4) Headache is nearly always present in patients with spontaneous (or idiopathic) CSF leakages (code 7.2.3) or posterior fossa tumours. 5) If the tumour is midline, it may systemic illnesses such as dehydration, diabetic coma, increase with coughing, straining, or sudden head hyperpnoea, or uraemia. Pachymeningeal contrast movement. 6) If the tumour is hemispheric, the pain is enhancement on MRI is a hallmark of intracranial typically felt on the same side of the head. 7) If the tumour hypotension54 (figure 5). Dilatation of epidural veins and is chiasmal, at the sella, the pain may be felt on the top of CSF leakage into the epidural space can be seen with MRI in the head. patients with “spontaneous” low CSF pressure.55 In specialised headache or pain clinics, brain tumours account for less than 1% of patients. There is significant Case report 5 overlap in the clinical characteristics of headaches caused by brain tumours and migraine-type or tension-type This 37-year-old man had a lumbar puncture because of recurrent paraesthesias in his left arm with fluctuating sensory loss. Multiple headaches. The following clues indicate that a thorough sclerosis was suspected. He developed severe postural headache neuroradiological examination is indicated: any headache of associated with nausea and photophobia. 3 days later, he complained of recent onset; previously existing headaches that have diplopia and presented with bilateral lateral rectus paresis. The diagnosis changed in character; a lock-sided headache not resembling of intracranial hypotension caused by CSF leakage after lumbar puncture the primary unilateral headaches; morning or nocturnal was made and he was treated with an epidural blood patch in the lumbar region. The headache resolved within 1 week. The bilateral VI headaches associated with vomiting in a patient who has no nerve palsy remitted gradually over 4 weeks. history of migraine. Intracranial neoplasm (code 7.4) Headache with neurological deficits and CSF Headache occurs at presentation in 36–50% of adults with lymphocytosis (“HaNDL”) (code 7.8) brain tumours and develops in the course of the disease in This syndrome is of unknown cause. It may mimic migraine 60%.52 Headache is typically generalised, of the dull, deep, with prolonged aura with the notable exception that there is aching type, and intermittent at first. Simple analgesics lymphocytosis on CSF examination. The episode may start 242 THE LANCET Neurology Vol 3 April 2004 For personal use. Only reproduce with permission The Lancet Publishing Group.
  7. 7. Diagnosis of focal headache Review with visual symptoms, but one-sided paraesthesias and Panel 2. Additional causes of painful ophthamoplegia59 weakness are more common. The headache may precede the neurological symptoms; it may be unilateral or bilateral and Orbital disease accompanied by nausea, vomiting, and sensoriphobia. Idiopathic orbital inflammation (pseudotumour) Although the headache lasts for several days, the Contiguous sinusitis neurological deficits take a few weeks to disappear Mucormycosis or other fungal infection completely. The episodes may recur several times in the Metastatic tumour same individual and are thought to be benign.10,57 Lymphoma or leukaemia Diabetic ophthalmoplegia Cranial neuralgia, nerve trunk pain, and Mononeuropathy deafferentation pain Multiple cranial-nerve palsies Trigeminal neuralgia (tic douloureux; code 13.1) Posterior fossa aneurysm Classical trigeminal neuralgia (code 13.1.1) is characterised Posterior communicating artery by very short (a few seconds up to 2 min) attacks of intense, Basilar artery electric-shock-like pain. Most trigeminal neuralgia starts in Giant cell arteritis the second (or third) division of the trigeminal nerve. More Ophthalmologic migraine women are affected than men (ratio three to two), and most Reproduced with permission from the BMJ publishing group. patients are older than 50 years. Pain occurs spontaneously or is triggered by stimuli such as washing, shaving, chewing, teeth brushing, or speaking. Painful episodes start and end eruption in the external auditory meatus (Ramsay-Hunt’s abruptly and may recur dozens of times or more in a day but zone) which is associated with facial nerve palsy in many interfere little with sleep. Remissions of variable duration are patients. described. The pain never crosses the midline, but a few Postherpetic neuralgia (code 13.15.2) is a chronic pain patients (<5%) have bilateral attacks.58 The pain often that commonly develops during the acute phase of infection induces reflex spasms of facial muscles on the affected side, and persists more than 6 months. It is a common sequel of hence the name “tic douloureux”. infection with herpes zoster and affects up to 50% of patients, On MRI or during surgical treatment of trigeminal particularly the elderly.60,61 Incidence is reduced by antiviral neuralgia, the trigeminal nerve root commonly looks treatment at the acute phase. The typical neuropathic pain is compressed or in intimate contact with a vessel. Vascular felt in the area formerly involved by the infection; it is decompression (Janetta’s procedure) is a highly effective treatment of drug-resistant trigeminal neuralgia, which is, in Panel 3. Diagnostic evaluation of Tolosa-Hunt syndrome59 many patients, a secondary pain disorder. For this reason, Haematological tests: the term “idiopathic” trigeminal neuralgia is replaced by Full blood count “classic” trigeminal neuralgia in the revised classification. Serum chemistry Trigeminal neuralgia with non-vascular causes—such as Erythrocyte sedimentation rate acoustic neurinomas, brainstem infarctions, or multiple C reactive protein sclerosis—is called symptomatic, trigeminal neuralgia (code Haemoglobin A1C 13.1.2). The main differences from the classic form are a Fluorescent treponemal antibody test younger age at onset, persisting ache between paroxysms, Antinuclear antibody and signs of sensory impairment in the distribution of the Anti-dsDNA antibody corresponding trigeminal division. Serum protein electrophoresis Antinuclear cytoplasmic antibody Tolosa-Hunt syndrome (code 13.16) Angiotensin converting enzyme This syndrome is characterised by episodic orbital pain with Cerebrospinal fluid test paralysis of the third, fourth, or sixth cranial nerves that Opening pressure resolves spontaneously after days or weeks, but may relapse Cell count and differential and remit. Protein There are several other causes of painful Glucose ophthalmoplegia (panel 2). Extensive clinical assessment is Culture: bacterial, fungal, mycobacterial needed to exclude inflammatory, infectious, vascular, or Serology neoplastic causes (panel 3).59 Angiotensin converting enzyme Neuroradiologial studies Herpes zoster (code 13.15.1) and postherpetic MRI, CT neuralgia (code 13.15.2) Cerebral angiography In 10–15% of patients with the virus, herpes zoster affects Biopsy the trigeminal ganglion, with particular affinity for the Nasopharynx ophthalmic division (80% of patients). Palsy of the third, Cavernous sinus fourth, or sixth cranial nerve is sometimes observed. Herpes Reproduced with permission from the BMJ publishing group. zoster may also involve the geniculate ganglion, with an THE LANCET Neurology Vol 3 April 2004 243 For personal use. Only reproduce with permission The Lancet Publishing Group.
  8. 8. Review Diagnosis of focal headache Search strategy and selection criteria Panel 4. Diagnostic hints for some disorders References for this review were identified by searches of Origin suggested by focal neurological signs or symptoms MEDLINE and citations in relevant articles by use of the search Cortical terms “headache”, “migraine”, “ophthalmoplegic”, “cluster”, “trigeminal-autonomic”, “ischemic”, “stroke”, “intracerebral”, Migraine with aura “hemorrhage”, “subarachnoid”, “vascular”, “malformation”, Cerebrovascular disorder “arteritis”, “dissection”, “cerebral”, “venous”, “thrombosis”, Supratentorial neoplasm “cerebrospinal”, “fluid”, “pressure”, “intracranial”, “neoplasm”, HaNDL “neurologic”, “deficits”, “lymphocytosis”, “HaNDL”, “neuralgia”, Cranial-nerve lesion “Tolosa”, “Hunt”, “herpes”, “zoster”, “post-herpetic”. Further- Tolosa-Hunt syndrome more, articles were identified through searches of the extensive Low CSF pressure files of the authors. Articles published until February 2004 were Basilar migraine included. Only papers published in English were reviewed. Herpes Zoster Autonomic dysfunction constant, moderate to severe, and many patients describe it as Trigeminal autonomic cephalagias burning. Paraesthesias and hypaesthesia are common. Carotid artery dissection Hemisphere distribution Conclusion Unilateral Many headache syndromes are associated with focal Tolosa-Hunt syndrome neurological symptoms or signs. Good knowledge of the Trigeminal neuralgia clinical phenotypes of primary headaches, a detailed history, Trigeminal autonomic cephalalgias and a thorough clinical examination are prerequisites for their Migraine with aura differential diagnosis. There are well-defined clinically relevant Herpes Zoster diagnostic hints on the headache as well as focal neurological Carotid artery dissection signs or symptoms for some of the disorders (panel 4). The HaNDL neurological symptoms produced by the migrainous aura are Bilateral probably the most characteristic and recognisable. However, Low/high CSF pressure structural lesions—such as vascular malformations—can Basilar migraine cause symptoms similar to migraine with aura, which Ruptured aneurysm highlights that in most patients with headache and focal Temporal arteritis neurological symptoms paraclinical investigations are Infratentorial neoplasm necessary. References 12 Mark AS, Casselman J, Brown D, et al. Cephalalgia 1991; 11: 123–27. 1 International Headache Society Classification Ophthalmoplegic migraine: reversible enhancement 24 Morales F, Mostacero E, Marta J, Sanchez S. Subcommittee. The International classification of and thickening of the cisternal segment of the Vascular malformation of the cerebellopontine angle headache disorders, 2nd edn. Cephalalgia 2004; oculomotor nerve on contrast-enhanced MR associated with SUNCT syndrome. 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