Medication overuse headache.

Medication overuse headache is a common feature underlying chronic headache, especially migraine. It also represents a major therapeutic challenge, especially in headache specialty clinics where it can represent the majority of patients. The syndrome remains under-diagnosed and the role of symptomatic medication overuse underestimated. Physicians should be properly educated in this area of pain, for prevention of this too often intractable syndrome could be improved. The basis of therapy is discontinuance of the abused medication. Additional treatment relies on a multifaceted approach that embraces management of psychiatric comorbidities and emphasizes patient education. Various pharmacological regimens, abortive and prophylactic, are available. Further scientific study is warranted to elucidate the ultimate mechanisms of this syndrome and define more effective treatments. This article gives detailed clinical description, tentative pathophysiologic explanation and therapeutic suggestions.

Amitriptyline in migraine prophylaxis.

In a controlled trial of amitriptyline hydrochloride in migraine prophylaxis, 100 patients received placebo for a four-week baseline period and then were randomized in double-blind fashion to therapy with amitriptyline (47 subjects) or placebo (53 subjects) for another four to eight weeks. Subjects received up to four 25-mg tablets of amitriptyline hydrochloride or identical placebo per day. Comparing the first and second four-week periods for each patient, the conditions of 55.3% of amitriptyline subjects as opposed to 34.0% of placebo subjects were greater than or equal to 50% improved and the difference between amitriptyline and placebo response rates was significant (P less than .05). Nondepressed subjects with severe migraine and depressed subjects with less severe migraine responded best to amitriptyline, whereas depressed subjects with severe migraine had little headache relief. Amitritryline is an effective antimigraine agent and the antimigraine effect seems relatively independent of antidepressant activity.

Prolonged encephalopathy with arsenic poisoning.

A case of prolonged reversible encephalopathy in a woman with arsenic poisoning is described. Previous descriptions of extended encephalopathy due to arsenic are rare.

Gliomatosis cerebri. Report of four cases and review of the literature.

Four cases of gliomatosis cerebri are reported that demonstrate the variability of the clinical course. A review of these and 32 cases from the literature revealed that the most striking finding was change in personality and mental status. Hemiparesis, ataxia, papilledema, headache, seizure, and brainstem signs were the next most common clinical findings. Laboratory and radiographic tests, including angiography and pneumoencephalography, often showed only minor and nonspecific changes in the face of profound mental deterioration. Increased intracranial pressure usually occurred late but was probably an important factor of the terminal course in most patients. The pathologic changes were typical, with diffuse infiltration of astrocytoma cells through brain stem, subcortical white matter, and, to a lesser extent, cerebral cortex.

Platelet aggregation, stroke, and transient ischemic attack in middle-aged and elderly patients.

Platelet aggregation was studied with optical density methods in a group of 39 patients with stroke or transient ischemic attacks (TIA) and in age, sex, and race-matched controls. The patients were divided at age 60 into young stroke patients and young controls (18 pairs) and old stroke patients and old controls (21 pairs). A semiquantitative measure of the threshold of phase II of platelet aggregation and distinct of disaggregation 3 minutes after peak aggregation were used as an index of platelet aggregability. Aggregability was significantly greater in young stroke patients than in young controls. Aggregability was similar in old stroke patients and old controls. Both old stroke patients and old controls were hyperaggregable compared with young controls, indicating that aggregability rises with age. This suggests that platelet aggregability is significant risk factor for stroke but is relatively more important in the younger than in the older stroke patient.

Platelet aggregability in migraine.

Employing optical density methods, platelet aggregation in response to 1.275, 1.7, and 3.4 micrometer adenosine diphosphate was tested in 46 patients with migraine and 46 controls matched by age, sex, and race. The migraine patients demonstrated platelet hyperaggregability when compared with controls, as manifested by a lower threshold for the platelet-release reaction and increased platelet stickiness following aggregation. There was no correlation of platelet hyperaggregability with the severity of migraine or with the occurrence of migraine-associated neurologic symptoms, suggesting that platelet hyperaggregability is a concomitant feature of the migraine syndrome but not dependent on the occurrence of the actual headache. As platelet hyperaggregability may predispose to development of intravascular platelet aggregates or mural thrombi, the hyperaggregability found here may help explain the increased incidence of stroke and heart attack in migraine patients that has been reported elsewhere.

Recurrent Guillain-Barré syndrome following influenza vaccine.

Two patients recovered from an attack of Guillain-Barré syndrome and then had a second attack of this disease, with a shorter latent period, following monovalent influenza vaccination. These cases suggest that an attack of Guillain-Barré syndrome may result in greater risk of future episodes of the syndrome in conjunction with exposure to influenza or other vaccinations.

Histoplasma meningitis with hyperactive suppressor T cells in cerebrospinal fluid.

Histoplasma meningitis usually occurs in conjunction with disseminated histoplasmosis. We studied a patient with common variable hypogammaglobulinemia who manifested meningitis without disseminated histoplasmosis. No histoplasma antibody was detected in cerebrospinal fluid (CSF) or blood. Evaluation of lymphocyte function in the blood revealed normal numbers of T cells with increased numbers of B cells. Most blood lymphocytes were identifiable, but most lymphocytes in CSF were null cells. Lymphocyte proliferative response to phytohemagglutinin or pokeweed mitogen was poor. T cells in CSF suppressed proliferative responses to histoplasma antigen by cells from blood or CSF, whereas T cells from blood did not. This difference suggested compartmentalization of T-cell function. The lack of humoral and cellular response to histoplasma in CSF may have allowed meningitis to develop, while the cellular response to histoplasma elsewhere prevented development of disseminated histoplasmosis.

Amitriptyline in the prophylaxis of migraine. Effectiveness and relationship of antimigraine and antidepressant effects.

Amitriptyline was evaluated as a prophylactic antimigraine agent in 110 patients with severe migraine. This agent improved the migraine more than 50 percent in 72 percent of patients and more than 80 percent in 57 percent of patients. Most of the 31 patients with less than 50 percent improvement had virtually no response. Depression, measured with the Zung Self-Rating Depression Scale, was absent in 40 patients, borderline in 53, and moderate to severe in 17. Overall, depression ratings improved minimally with therapy. There was a weak relationship between improvement in depression and improvement in migraine. Subgroups with a stronger correlation of these could not be found. This work suggests that amitriptyline is effective in migraine prophylaxis and that it has a primary effect on migraine that is relatively independent of its antidepressant action.

Characteristics of life headache histories in a nonclinic population.

A detailed questionnaire concerning life history of headache and its characteristics was administered to 1,809 nonmedical volunteers. Questions dealt with severity of headache, the nature of preceding and accompanying phenomena (nausea, visual scotomata, neurologic symptoms), precipitating factors, and history of other illness. For the total sample and in the 25 to 39 age group, severe or disabling headaches were significantly more frequent in women and mild headaches were significantly more common in men. Migraine characteristics were common with mild headache. An association between hypertension and severe headache was found in women, between asthma and severe headache in men.

Modulation of spinal synaptic transmission by beta-melanocyte stimulating hormone (beta-MSH).

Synaptic modulation refers to altered excitability of a synapse by a substance that does not produce a spike potential at the synapse. Available evidence points to the conclusion that beta-melanocyte stimulating hormone (beta-MSH) modulates synaptic transmission through monosynaptic pathways in the cat spinal cord. Earlier evidence is reviewed, and new data are presented. In the first experiments populations of cells contributing to a knee jerk were studied using the Lloyd preparation, and MSH was found to increase the monosynaptic reflex. With intracellular single unit recording techniques, beta-MSH was found to facilitate recovery from synaptic transmission. With extracellular single unit recording techniques and iontophoretic methods for drug application, beta-MSH has been found to increase the probability of generation of single spike potentials by alpha-motoneurons in response to orthodromic stimulation. Administration of beta-MSH did not cause spontaneous discharge of alpha-motoneurons. The physiological and pharmacological importance of synaptic modulation is discussed.

Modulation of cat monosynaptic reflexes by substance P.

Substance P (SP) applied by iontophoresis at different current strengths to single motoneurons of cat spinal cord did not cause these units to discharge. SP produced a gradual and prolonged change in synaptic excitability as measured by response to dorsal root stimulation. The effect outlasted application of SP. The lowest effective dose of SP diminished motoneuron response to dorsal root stimulation (inhibitory modulation). Doses 2-4 times as great enhanced the response to dorsal root stimulation (facilitatory modulation) without causing the motoneuron to discharge spontaneously. These observations suggest that one physiological role of SP is modulation of synaptic transmission, i.e. alteration of efficacy of transmission without acting as a primary transmitter at the postsynaptic membrane.

Visualization of brain iron by mid-field MR.

Brain iron was visualized on a mid-field (0.5 T) scanner using a spin-echo pulse sequence. Methemoglobin was hyperintense on T1- and T2-weighted images. Deoxyhemoglobin, hemosiderin, and ferritin were seen as decreased intensity on T2-weighted images. The spin-echo pulse sequences were improved for identification of deoxyhemoglobin, hemosiderin, and ferritin by prolonging the TR to 3000 msec and the TE to 80-120 msec. Phase-encoding artifacts at the level of the sylvian fissures caused increased noise, obscuring the brain iron in the lentiform nuclei with the TE of 120 msec. This artifact was substantially reduced or eliminated by lowering the TE to 80 msec, changing the phase-encoding gradient to the Y axis, or using additional pulsing in the slice and read gradients. Use of either the improved spin-echo or gradient-echo pulse sequences on a mid-field MR scanner provides improved evaluation of brain iron.

Headache to worry about.

The headache to worry about is one that is unique or different from headaches which the patient has suffered in the past. The association with the headache of meningismus or of focal neurologic symptoms of oculoparesis, other cranial nerve palsies, hemiparesis, or loss of consciousness are particularly worrisome, especially if onset is recent and acute. Headaches related to arteritis or vasculitis usually have a slower subacute course but may also produce focal neurologic deficits. For subjects over 50 years old, temporal arteritis is always a consideration and any new type of headache requires testing of the sedimentation rate to rule out this treatable but potentially devastating problem.

Onset of neurologic deficits after treatment with dihydroergotamine in a patient with sagittal sinus thrombosis.

A woman with a 7-year history of intermittent migraine had 3 months of gradually worsening headaches. Initial neurologic examination including fundus examination was normal, and initial head computerized tomographic (CT) scan and magnetic resonance imaging (MRI) were thought to be normal. The patient was given dihydroergotamine (DHE-45), 1.0 mg, intravenously for relief of headache. Five hours later, she complained of severe diffuse headache and nausea. Neurologic examination showed left arm weakness and sensory loss, blurring of the left optic disc, and bilateral Babinski signs. Cerebral arteriography demonstrated thrombosis of the sagittal sinus, which in retrospect was present on the initial contrast CT scan and MRI scan. The patient's deficits worsened, and she eventually died 20 days later as a result of cerebral infarctions and increased intracranial pressure, despite attempts at selective thrombolysis of the sagittal sinus. DHE has potent venoconstrictive effects. We suspect that DHE helped precipitate neurologic deterioration in this patient with sagittal sinus thrombosis.

Dystonia and tremor in spasmodic torticollis.

The occurence of extranuchal dystonia, facial spasm, parkinsonian symptoms (facial masking, bradykinesia, rigidity), tremor and family history of tremor was tabulated in a group of 30 patients with IST. The incidence of extranuchal dystonia increased as severity of IST increased. There was a strong trend for severity of extranuchal dystonia to increase as severity of torticollis increased, which was significant (p less than 0.001). There was a similar trend for severity of facial spasm to increase with increasing severity of torticollis (p less than 0.025). Parkinsonian features were seen in 10 of 30 patients, and in three the diagnosis of Parkinson's disease could be entertained. Tremor was seen in 26 of 30 patients being mild in 12, moderate in 11, and severe in three. A family history of tremor was present in 16 of 28 cases for whom history was available (12 primary, four secondary relations). The results are most consistent with the hypothesis that IST is a variant of DMD with tremor as an integral part of the disease and tremor represents a forme of the disease in family members.

Antiplatelet therapy in the treatment of cerebrovascular disease.

Aspirin and the new agent ticlopidine have been the most thoroughly evaluated of the platelet-antiaggregating drugs used for the prevention of stroke and other vascular events. Numerous trials have shown aspirin to be effective in reducing the risk of myocardial infarction (MI), recurrent transient ischemic attacks, stroke, and vascular death in men at high risk for these events. Primary prevention trials have shown that aspirin reduces the risk of MI in healthy men over 50 years of age but does not reduce the risk of stroke. Two large, multicenter trials have shown that ticlopidine is effective in reducing the risk of fatal and nonfatal stroke in both men and women. Ticlopidine may also be effective in reducing the risk of recurrent stroke in patients who have had a completed thromboembolic stroke.

"Numb, clumsy hands" and high cervical spondylosis.

Thirteen patients with cervical spondylosis and high compressive myelopathy between C-3 and C-5 presented with a distinctive clinical syndrome of "numb, clumsy hands" and stereoanesthesia of the hands. Loss of position and vibration sense was much more severe in the hands than in the legs. Relative sparing of primary sensory modalities and motor and bladder functions were other features. Most patients were incorrectly diagnosed at first and cervical myelography was the critical diagnostic test. Pathology was confirmed surgically or at autopsy. Early recognition and treatment resulted in lessened disability. The syndrome is a distinctive and unusual manifestation of high cervical myelopathy, and it has seldom been reported associated with cervical spondylosis.