Review of problems arising from communication difficulties in headache practice.

Literature review and assessment of practice experience.

Advances in understanding of the pathophysiology of migraine and the availability of specific acute therapies have given migraine sufferers access to effective treatment and physicians a wide array of therapeutic alternatives. There remains uncertainty about the best drug group for any given patient and about which triptan to use when and in which formulation; about patient preference and satisfaction; about interpretations of pivotal trials and meta-analyses; and about the relevance of large group efficacy and safety data to the individual patient. The clinician may be daunted by the array of triptans with choices of dosage and multiple formulations and will likely learn how to use two or three of them at most, as in depression and hypertension. In the context of the wide array of choices and the complexities of assessing responses and patient preferences, this paper attempts to provide a framework for incorporating the evidence with clinical experience and for communicating these concepts effectively.

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Even when an appropriate recommendation is determined, therapy may fail unless the doctor patient relationship permits open communication, time for questions and answers and time for instruction on how to use a given medication, and its probable effects. Translating evidence into patient-friendly language is a skill as necessary as that of making the clinical decision itself. Tools are available that can support this effort and aid in creating an environment of “partnership”.

Six/second spike waves, 14 and 6/second positive spikes and small sharp spikes are apiculate paroxysmal rhythms in the electroencephalogram, thought to be of no diagnostic importance. The cortical origin of these discharges is documented in this report.

These waveforms were assessed in recordings from the surface of the cerebral cortex using implanted subdural electrodes in 61 patients monitored for possible epilepsy surgery.

Eight patients had 6/second spike wave, four had 14 and 6/second positive spikes and 3 had small sharp spikes. The 6/second spike waves were localised to the posterior cingulate gyrus, a more restricted region than would be predicted from scalp recordings and the 14 and 6/second spikes to the posterior mesial temporal cortex. Small sharp spikes were more widely distributed but also predominated in the posterior mesial temporal area. None of the discharges were congruent with the focus of seizure origin and no interaction with other interictal spikes was found.

These benign paroxysmal rhythms can appear incidentally in the electrocorticograms of patients with focal epilepsy and should not be confused with focal pathological spike activity or considered to be of any value in localizing the seizure focus.

To evaluate the safety and efficacy of stereotactic radiosurgery (SRS) compared to fractionated stereotactic radiation therapy (FSRT) for meningiomas treated over a seven year period.

Of the 53 patients (15 male and 38 female) with 63 meningiomas, 35 were treated with SRS and the 18 patients with tumors adjacent to critical structures or with large tumors were treated with FSRT. The median doses for the SRS and the FSRT groups were 1400 cGy (500- 4500 cGy) and 5400 cGy (4000-6000 cGy) respectively. Median target volumes for SRS and FSRT were 6.8 ml and 8.8 ml respectively. The median follow-up for the SRS and FSRT groups were 38 months (4.1-97 months) and 30.5 months (6.0-63 months) respectively.

The five-year tumor control probability (TC) for benign versus atypical meningiomas were 92.7% vs. 31% (P=.006). The three-year TC were 92.7% vs. 93.3% for SRS vs. FSRT groups respectively (P=.62). For benign meningiomas, the three-year TC were 92.9% vs. 92.3% for the SRS group (29 patients) vs. FSRT group (14 patients) respectively (P=.77). Two patients in the SRS group and one in the FSRT group developed late complications.

Preliminary data suggest that SRS is a safe and effective treatment for patients with benign meningiomas. Fractionated stereotactic radiation therapy with conventional fractionation appeared to be an effective and safe treatment alternative for patients not appropriate for SRS. A longer follow-up is required to determine the long-term efficacy and the toxicity of these treatment modalities.

Metachromatic leukodystrophy (MLD) is a genetic neurodegenerative disorder resulting from a deficiency of arylsulfatase A. Late onset forms are relatively rare. Central nervous system (CNS) involvement is characteristic at all ages.

A patient in her late 40s with peripheral neuropathy was assessed by EEG, evoked potentials, CTand nerve conduction studies. Nerve and muscle biopsy samples were investigated by electron microscopy. Arylsulfatase A activity in leukocytes and excreted cerebroside sulfate were determined. The arylsulfatase A gene was investigated for mutations using polymerase chain reaction (PCR) and DNAsequencing. The identified mutation was expressed transiently in African green monkey kidney (COS) cells to determine the effect of the mutation on arylsulfatase A activity.

Central nervous system functions were normal. Nerve conduction velocities were decreased. Sural nerve biopsy showed inclusions typical of MLD. Arylsulfatase A was less than 5% of normal. A homozygous mutation thr286pro was identified in the arylsulfatase A gene and demonstrated to be deleterious through transient expression studies.

Our patient has a progressive peripheral neuropathy but has apparently intact CNS function at her present age of 57 years. Biochemical, physiological and pathological findings are consistent with a diagnosis of MLD. A homozygous mutation, thr286pro, found in her arylsulfatase A gene, decreased enzyme activity to a level consistent with a late onset form of MLD.

Outpatient surgery saves the risk of nosocomial complications and health care dollars. Patients undergoing lumbar microsurgical discectomy are excellent candidates for outpatient surgery. The object of this study was to examine the feasibility of performing lumbar microdiscectomy on an outpatient protocol and to examine the potential savings associated with such a protocol.

From February 1997 to September, 2001, 122 consecutive patients of the senior author were entered into a protocol of outpatient lumbar microdiscectomy. Only elective cases were considered for this study. Patients were excluded if they had significant co-morbidities, lived a significant distance out of town, or if their surgery was scheduled too late in the day. Success was defined as discharge home from the day-surgery unit approximately four hours after surgery.

During the study period, 150 elective lumbar microdiscectomies were performed. Twenty-four patients were excluded based on the above criteria and four patients requested not to participate in the study. Of the remaining 122, 116 successfully completed the protocol (95.1%). Six patients were admitted from the day surgery unit; two patients with dural tears and four patients with anaesthetic side-effects. No patient was readmitted to hospital after discharge and no complications of early discharge were observed. There was a total reduction in hospitalization of 1.2 nights per elective procedure considering the 150 patients, when compared with the hospitalization times prior to outpatient lumbar microdiscectomy.

Lumbar microdiscectomy can be performed safely as an outpatient procedure, resulting in a substantial reduction in hospitalization times.

To delineate factors associated with the successful endovascular treatment of extracranial carotid dissections, the authors review their management of 13 cases.

The records of 12 patients with 13 dissections were assessed with reference to mechanism of dissection, preoperative symptoms, presence of a pseudoaneurysm, treatment success, and etiology of treatment failure. Patients were followed prospectively and included six men and six women, ranging in age from 27 to 62 years.

Angioplasty and stenting were performed successfully in 11 of 13 procedures (10 of 12 patients). Follow-up in these 10 patients demonstrated excellent patency through the stented segment in nine of the 11 treated vessels. Two patients, both of whom suffered their original dissection as a result of endarterectomy, required further angioplasty and stenting for stenosis outside the previously treated arterial segment. Regarding the treatment failures, a stent deployment device could not navigate a tortuous loop in one, while a microwire could not be advanced beyond a pseudoaneurysm in the second. Six patients had pseudoaneurysms, four of which were treated only with stenting across the dissected arterial segment. All pseudoaneurysms treated in this fashion resolved. No permanent complications occurred as a result of endovascular therapy.

Angioplasty and stenting can be performed safely to manage carotid dissection. A pseudoaneurysm or tortuous anatomy can preclude therapy although the former typically resolves if angioplasty and stenting are feasible. Dissections secondary to endarterectomy may be associated with a higher rate of restenosis after stenting and may require further treatment.

We describe nine females with Rett Syndrome (RS), aged 14 to 26 years. All had had developmental delay before the end of their first year and had subsequently regressed to profound dementia with apraxia, ataxia, irregular respirations and often also seizures.

The Revised Gesell developmental assessment and Alpern-Boll Developmental Profile were used in modified form. Volumetric measurements of basal ganglia using MRI were compared with the findings in nine age-matched volunteer females. Positron emission scans with [18F]-6-fluorodopa and [11C]-raclopride were performed under light anesthesia with intravenous Propofol, and the findings were compared with those in healthy control girls. Bidirectional sequencing of the coding regions of the MECP2 gene was investigated in blood samples for mutational analyses.

The RS females functioned at a mental age level ranging from about 4 to 15 months. The scores correlated with height, weight and head circumference. Magnetic resonance scans of basal ganglia showed a significant reduction in the size of the caudate heads and thalami in the Rett cases. Positron emission scans demonstrated that the mean uptake of fluorodopa in RS was reduced by 13.1% in caudate and by 12.5% in putamen as compared to the controls, while dopamine D2 receptor binding was increased significantly by 9.7% in caudate and 9.6% in putamen. Mutations in the coding regions of the MECP2 gene were present in all nine patients. No significant correlation between type and location of mutation and volumetric changes or isotope uptake was demonstrable.

Our findings suggest a mild presynaptic deficit of nigrostriatal activity in Rett syndrome.

Recently described nonmotor fluctuations may cause disability in Parkinson's disease patients. These fluctuations are generally grouped as sensory, autonomic and psychiatric. The clinical spectrum and frequency of these fluctuating symptoms are not well-described.

We studied the relationship of nonmotor fluctuations with motor symptoms and determined the influence of age at disease onset, duration of disease, dosage and duration of levodopa treatment in the appearance of nonmotor fluctuations.

Statistical analysis showed a relationship of disease-related parameters with sensory and autonomic fluctuations but psychiatric fluctuations were only found to be associated with the duration of levodopa usage. The nonmotor fluctuations included in the study were observed during “on” periods as well as “off” periods.

Nonmotor fluctuations had variable presentations. Moreover, their co-appearance with different types of motor fluctuations may be linked to the effect of other neurotransmitter systems acting synchronously with dopamine. Risk factors for sensory and autonomic fluctuations in patients with Parkinson's disease were early age of disease onset, longer duration and higher dose of levodopa use. Psychiatric fluctuations were only associated with higher doses of levodopa.

To evaluate the investigation and treatment of patients with a diagnosis of transient ischemic attacks (TIA) in the emergency department (ED) a tertiary care teaching hospital with a neuroscience referral program.

A chart review was conducted in the hospital. Consecutive ED charts with a diagnosis of TIA were included; each was reviewed by independent coders using a standardized data form.

Two hundred and ninety-three TIAcharts were reviewed; the gender ratio was 1:1 with a mean age of 66 years. Most patients (75%; 95% CI: 70, 80) were evaluated by ED physicians; the remaining patients were seen directly by referral services. The median time from symptom onset to ED arrival was 2.9 hours and the duration of symptoms was 4.6 hours. Most patients received CT scans (81%; 95% CI: 73, 85), complete blood counts (74%; 95% CI: 68, 79), and electrocardiograms (75%; 95% CI: 70, 80) in the ED. In 16% (95% CI: 13, 22) a carotid doppler was performed and in 26% (95% CI: 21, 31) an outpatient doppler was booked. Among those who were discharged (75%; 95% CI: 70, 80), antithrombotic medications were not prescribed to 28% (95% CI: 22, 34).

Practice variation exists with respect to the investigation and treatment of TIAs in this tertiary-care teaching hospital. Carotid doppler investigation and use of anti-platelet therapy for patients with TIAare suboptimal. Clinical practice guidelines and rapid assessment TIAclinics may change these results.

Aging impacts microvessels in a number of tissue beds. Vasopressin acts as a vasoconstrictor in most blood vessels but may also cause vasodilation. We evaluated the role of aging and vasopressin in the regulation of nerve blood flow (NBF) in rat peripheral nerve.

We undertook a dose-response study to examine the impact of aging on resting NBF and its vasoreactivity to vasopressin. Nerve blood flow was measured using microelectrode hydrogen polarography. Argininevasopressin was administered both intra-arterially and topically.

In young adult rats (two months old) topical epineurial application of arginine-vasopressin produced a concentration-dependent reduction of NBF (ED50= 3.8 X 10-5 mol/L). Intra-arterial arginine-vasopressin also reduced NBF. Nerve blood flow was lower in aged rats (12 months old) and less responsive to topically applied vasopressin. The aging group had significantly higher concentrations of vasopressin in plasma than did the younger group.

The results suggest that vasopressin constricts vessels in peripheral nerve and that there is an age related decline in the vasoconstrictive response to vasopressin. There may be a reduction in receptor sensitivity in vascular smooth muscle cells in peripheral nerve with increasing age.

Spontaneous intracranial hypotension (SIH) is a neurologic syndrome of unknown etiology, characterized by features of low cerebral spinal fluid (CSF) pressure, postural headache and magnetic resonance imaging (MRI) abnormalities.

Four symptomatic cases of SIH presented to our institution over a six-month period. Magnetic resonance imaging studies were performed in all four cases. Diagnostic lumbar puncture was done in all except one case.

All of the patients on whom lumbar punctures were performed demonstrated low CSF pressure and CSF protein elevation with negative cultures and cytology. Three out of the four patients exhibited MRI findings of diffuse spinal and intracranial pachymeningeal gadolinium enhancement and extradural or subdural fluid collections. One patient had no MRI abnormalities despite prominent postural headache and reduced CSF pressure at lumbar puncture. All patients recovered with intravenous fluids and conservative treatment.

Magnetic resonance imaging abnormalities are found in most, but not all patients, with SIH. Cerebral spinal fluid abnormalities can be detected even in patients with normal MRI studies. It is important to recognize the variability of imaging results in this usually benign disorder.

Convulsive status epilepticus (CSE) is a common neurological emergency. Our objectives were to study children with recurrent nonfebrile CSE to assess the evidence for focal origin.

Series of 18 children with recurrent CSE and intractable epilepsy were identified by chart review. Clinical, radiological, and EEG data were reviewed. Focal structural abnormalities were identified on MRI and CT images by one neuroradiologist who was unaware of the clinical details.

The patient's ages ranged between 6-22 years (mean 15.3, SD 4), and 67% were males. Most children (89%) had a severe cognitive and / or behavioural disorder. Most patients (89%) had multiple seizure types and 95% of these were partial seizures. Twelve (67%) children had at least one episode of CSE with focal features identified clinically. Focal brain abnormalities were detected on 18% and 55% of CTand MRI films respectively. Overall, 53% had a focal abnormality on structural neuroimaging. Interictal EEG revealed focal or multifocal abnormalities on at least one occasion in 94% and 22% of patients respectively. Overall, 17 patients had focal features on at least one EEG. Thirteen ictal EEGs were recorded on 11 (61%) patients. Ten (91%) of these recordings revealed a focal onset.

Many handicapped children with recurrent CSE have focal clinical, radiological, or electrographic features. This supports a focal origin for CSE in most children with intractable epilepsy.

For the conduct of controlled clinical trials, epidemiologic surveys or even of medical practice of varieties of peripheral neuropathy, the usefulness, error rate and cost-effectiveness of scannable case-report forms has not been studied. Materials and

The overall performance, the frequency of the problems identified and corrected, and the time saved from use of a standard paper case report form was evaluated in multicenter treatment trials, single center epidemiologic surveys and in our neurologic practice. The paper case report form (Clinical Neuropathy Assessment [CNA]) for pen entry at study medical centers for patient, disease and demographic information (Lower Limb Function [LLF] and Neuropathy Impairment Score [NIS]) can be faxed to a core Reading and Quality Assurance Center where the form and data is electronically and interactively evaluated and corrected, if needed, by participating medical centers before electronic entry into database.

1) The approach provides a standard, scannable paper case report form for pen entry of neuropathy symptoms, impairments and disability at the bedside or in the office which is retained as a source document at the participating medical center but a facsimile can be transferred instantaneously, its data can be programmed, interactively evaluated, modified and stored while maintaining an audit trail; 2) it allowed efficient and accurate reading, transfer, analysis, and storage of data of more than 15,000 forms used in multicenter trials; 3) in 500 consecutive CNA evaluations, software programs identified and facilitated interactive corrections of omissions, discrepancies, and disease and study inconsistencies, introducing only a few readily identified and corrected entry errors; and 4) use of programmed, as compared to non-programmed assessment, was more accurate than double keyboard entry of data and was approximately five times faster.

Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12).

A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 (51Cr) release assay.

Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2, GM-CSF, and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells.

PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of tumor subclones with limited antigenic spectra during retrovirus-mediated gene transfer.

Pulmonary and respiratory muscle function impairment are common in patients with Parkinson's disease (PD). However, dyspnea is not a frequent complaint among these patients, although it is well documented that the intensity of dyspnea is related to the activity and the strength of the respiratory muscles.

We studied pulmonary function, respiratory muscle strength and endurance and the perception of dyspnea (POD) in 20 patients with PD (stage II and III Hoehn and Yahr scale) before and after their first daily L-dopa dose. Respiratory muscle strength was assessed by measuring the maximal inspiratory and expiratory mouth pressures (PImax and PEmax), at residual volume (RV) and total lung capacity (TLC) respectively. The POD was measured while the subject breathed against progressive load and dyspnea was rated using a visual analog scale.

Respiratory muscle strength and endurance were decreased and the POD was increased during the off medication period compared to normal subjects. There was a nonsignificant trend to an increase in PImax, PEmax and endurance after L-dopa intake. The POD of PD patients decreased (p<0.05) following medication, although, it remained increased (p<0.01) as compared to the normal subjects. Even if patients had spirometry data showing a mild restrictive pattern, before medication, both forced vital capacity (FVC) and forced expiratory volume (FEV)1 remained almost identical after L-dopa intake.

Patients with PD have higher POD, compared to normal subjects and this increased perception is attenuated when the patients are on dopaminergic medication. The change in the POD is not related to changes in respiratory muscle performance or pulmonary functions. A central effect or a correction of uncoordinated respiratory movements by L-dopa may contribute to the decrease in POD following L-dopa treatment.