Direction of temperature control in the thermal biofeedback treatment of vascular headache.

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p = .003) reduced as was HA medication consumption. There were no differential reductions in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.

Platelet morphology in Parkinson's disease: an electron microscopic study.

There are no peripheral diagnostic markers for Parkinson's disease (PD). However, recent studies of platelets in PD patients indicate that mitochondrial and monoamine oxidase function may be abnormal. This investigation examines platelets in PD from a morphological standpoint utilizing transmission electron microscopy (EM). Fourteen PD patients (seven treated, seven untreated) and seven age matched controls had platelets separated from other blood components, fixed in a standardized fashion and examined by EM. Platelets (in the activated form because they were collected in glass tubes) were evaluated at magnifications of 15,000x and 40,000x. Abnormalities observed in treated and untreated PD patients included the presence of numerous large intracytoplasmic vacuoles formed from the open canalicular system. Morphometric examination performed at 40,000x magnification indicated that the mean area of vacuoles and the cytoplasmic volume percent of platelets occupied by vacuoles were significantly greater in PD (p < 0.05) than controls. However, differences observed between treated and untreated PD groups suggest that these changes could be caused by the disease or the treatment or both. No abnormalities were found in relation to mitochondria, storage granules and glycogen. From EM assessment, we conclude that platelets in PD are morphologically abnormal.

Preliminary results from the self-regulatory treatment of high-medication-consumption headache.

Data are presented from a prospective clinical replication series of ten consecutive high-medication headache patients who presented for nondrug treatment of their headaches. For the first eight, an attempt was made to withdraw the patients from medication, with the assistance of relaxation training, prior to entering a comprehensive self-regulatory treatment program. For the last two, drug withdrawal accompanied the treatment. Six of the ten patients showed clinically significant reductions in headache activity, which held up over follow-ups of up to 12 months. Psychological tests provide some discrimination between success and failures.

The role of home practice in thermal biofeedback.

The role of regular home practice of hand warming was examined in the thermal biofeedback (TBF) treatment of vascular (migraine and mixed migraine and tension) headache (HA) by giving 12 sessions (over 6 weeks) of TBF to two groups of vascular HA patients (n = 23 per group). One group was asked to practice regularly at home with a home trainer between clinic sessions, whereas no mention of practice was made to the other group. A third group merely monitored HAs. Treatment was superior to no treatment. There was no advantage for the group receiving home practice, either in headache reduction or in acquisition of the hand-warming response.

A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache.

Seventy-six patients with vascular (migraine or mixed migraine and tension) headache (HA) participated in a controlled evaluation of a minimal-therapist-contact, largely home-based, treatment program which combined relaxation (R) training with thermal biofeedback (TBF). One group received TBF + R administered in 3 office visit over 8 weeks, supplemented by audio tapes and manuals. A second group received the TBF + R plus instruction in cognitive stress coping techniques, all of which was administered in 5 office visits over 8 weeks. A third group monitored headache activity for 8 weeks. Evaluations, based on 4 weeks of HA diary at pre-treatment and after treatment, revealed significantly greater reductions in HA activity and medication consumption for both treated groups than the HA monitoring controls who did not change. Significantly more of the treated patients had clinically significant reductions in HA activity than the controls. The two treated groups did not differ on any measure.

Axonal regrowth in the amyelinated optic nerve of the myelin-deficient rat: ultrastructural observations and effects of ganglioside administration.

It has been postulated that myelin degradation products may inhibit regrowth of mammalian central axons and that central nervous system (CNS) myelin and oligodendrocytes may constitute a "nonpermissive substrate" for axonal growth. To address these issues, we utilized an X-linked rat mutant, myelin-deficient or md. In the optic nerve of this mutant, 40 days and more postnatally, normal myelin is absent and oligodendrocytes are few (Dentinger et al. Brain Res. 344:255-266, 1985). Twenty-eight days before sacrifice, we operated on four groups of 50-day-old md rats and age-matched normal littermates according to the following protocols: 1) unilateral intraorbital optic nerve crush; 2) beginning within 1 hour of nerve crush, daily intraperitoneal injection of GM1 ganglioside (20 mg/kg) dissolved in phosphate-buffered saline (PBS); 3) daily intraperitoneal injection of PBS alone, also begun within 1 hour of nerve crush; 4) severance of the optic nerve immediately behind the papilla 16 or 21 days after the primary crush lesions. Additionally, normal and md rats were killed 4 and 14 days after unilateral optic nerve injury. Nerves of unoperated md rats and their normal littermates were also processed. In the operated animals that did not receive GM1, ultrastructural analysis 4, 14, and 28 days after lesioning revealed that md optic nerves contained significantly greater numbers of regenerating axons, including growth cones and varicosities, than nerves of normal rats. Notably, 28 days postoperatively, (group 1), regenerating axons were still abundant in md nerve, whereas, in nerves of normally myelinated littermates, axonal numbers were diminished markedly. Regenerating optic axons of both md and normally myelinated rats were oriented by linear astrocytic arrays and often were enclosed by astrocytic cytoplasm. In normal littermates, GM1 administration (group 2) induced a significant increase in the number of axons within the operative lesion. Paradoxically, GM1 inhibited the ordinarily robust regeneration of md axons. PBS-injected md and normal rats (group 3) showed no significant differences from noninjected, operated animals. Severance of the nerve at the papilla (group 4) 7-12 days before sacrifice confirmed the origination of axonal regrowth by retinal ganglion cells. The data provide in vivo support for a role of myelin breakdown products or the secretory products of oligodendroglia in the inhibition of regenerative axonal sprouting within mammalian CNS.

Neurological evaluation of chronic headache patients: is laboratory testing always necessary?

A review of records was conducted to examine the utility of doing routine laboratory testing (EEG and skull X rays) versus testing at the discretion of the attending neurologist on patients presenting for the nonpharmacological treatment of chronic headache. A total of 278 patients underwent neurological evaluation as part of a routine assessment prior to beginning self-regulatory treatment for headache. The first 112 subjects received routine laboratory tests of EEG and skull X-ray films. The second set of 166 subjects received laboratory tests only when deemed necessary by the neurologist. The rate of abnormal EEG in chronic headache sufferers was no greater than that found in the normal population, and only one or two potentially serious abnormalities were found on any laboratory test. A higher rate of abnormality was found when the CT scan was used in conjunction with clinical judgment. The majority of clients with abnormal laboratory tests (most of which were mildly abnormal) still saw substantial headache reduction with self-regulatory treatment for chronic headache. The authors suggest that routine laboratory testing may not be necessary and should be left to the discretion of a qualified neurologist.

Cytological and cytochemical (RNA) studies on rubral neurons after unilateral rubrospinal tractotomy: the impact of GM1 ganglioside administration.

The rubrospinal tract (RST) was cut unilaterally at C2-3 segment in 21 rats that were killed 3, 7, 10, 14, 28, 60, and 90 days later. Additionally, 14 rats, killed 14 or 28 days after lesioning, were treated postoperatively by daily intraperitoneal injections of GM1 ganglioside. Six unoperated, untreated rats served as controls. In untreated animals, axotomized neurons of the magnocellular division of the red nucleus (RN) exhibited cytoplasmic, nuclear, and nucleolar atrophy 7-10 days postoperatively. Atrophy progressed through the 90th postoperative day. Regression analyses disclosed a bimodal pattern to cytoplasmic and nucleolar atrophy, with an initial rapid phase changing to a slower but progressive mode from 14 days postoperatively. Nuclear atrophy proceeded in a unimodal manner. GM1 treatment did not affect these atrophic processes. Neuronal loss did not occur in the axotomized RN through the 60th postoperative day. Axotomized neurons of untreated rats showed significant and progressive reductions in mean somal (cytoplasmic) and nucleolar RNA from, respectively, the 7th and 14th postoperative day. GM1 partly prevented these RNA losses. Both in treated and untreated rats, spinal cord lesions contained many axonal sprouts 2 to 4 weeks after surgery, but newly generated axons did not traverse the rostro-caudal extent of any lesion.

The refractory headache patient--I. Chronic, daily, high intensity headache.

Two studies on patients with Chronic, Daily, High Intensity Headache (CDHIHA) are presented. In the first, their response to various self-regulatory (biofeedback, relaxation) treatments was compared to that of case controls matched for age, duration and Ad Hoc Committee diagnoses who had 1-2 headache-free days per week (Group II) and 3-5 headache-free days per week (Group III). The CDHIHA patients had a significantly poorer response to treatment (12.7 vs 49.8% improvement for Groups II and III combined). In the second study, the psychological profiles of an enlarged sample of CDHIHA patients were compared to matched case controls from Group II and Group III. The CDHIHA patients tended to be more anxious, more hysterical and to have more non-headache somatic complaints than Groups II and III combined.

The refractory headache patient--II. High medication consumption (analgesic rebound) headache.

'Analgesic rebound headache' is identified by habituation of an individual to pain reducing medication, the exacerbation of headache pain a few hours after medication consumption and a marked increase in headache frequency and intensity for several weeks after medication is discontinued. We describe three studies undertaken to clarify the existence and characteristics of this proposed headache syndrome. In Study 1 we compared a group of headache sufferers who consume large amounts of analgesic medications to headache sufferers who did not consume excessive analgesics. It was found that the two groups did not differ on age, duration of headache problem or gender. However, the groups did differ on subjective headache pain (with the high medicators experiencing more headache pain than low medicators) and diagnosis (with high medicators being more likely to have a muscle contraction component to their headaches). In an analysis of drug use within the high medication group, it was found that 91% were taking some kind of analgesic and that a majority (84%) were taking more than one type of medication. In Study 2 we found that the group of high medicators were not as successful in reducing headache activity as a result of a self-regulatory behavioral treatment as the matched controls. Furthermore, there was a direct relationship between reduction and treatment success in the high medication consuming population. Lastly, in Study 3 we examined the current psychological functioning of the two groups; no differences were found between the two groups indicating the lack of 'addictive' personality characteristics as an explanation for the high medicating population. These findings all support the existence of a sub-population of headache sufferers who consume excessive amounts of analgesic medication and who are relatively refractory to behavioral treatment.

Nemaline myopathy associated with hypertrophic cardiomyopathy.

Nemaline myopathy is not usually considered to involve cardiac muscle and rarely is associated with nocturnal hypoventilation. We report a boy, 5 1/2 years of age, with nemaline myopathy who presented with respiratory failure. Echocardiography demonstrated the septum to left ventricular posterior wall ratio to be increased which is consistent with a hypertrophic cardiomyopathy. Because of nocturnal hypoventilation, tracheostomy was placed for ventilatory assistance. A process involving both muscle and nervous tissue may underlie this congenital myopathy; routine cardiac and pulmonary function evaluations may be indicated in these patients.

Brain hemosiderin and superficial siderosis of the central nervous system.

Brain tissue from five patients with superficial siderosis of the central nervous system was examined by immunocytochemistry for ferritin, glial fibrillary acidic protein (GFAP), alpha 1-antitrypsin, and alpha 1-antichymotrypsin, and by lectin affinity cytochemistry with biotinylated Ricinus communis agglutinin-1 (RCA-1). The sections were pretreated with 2,2'-dipyridyl and sodium hydrosulfite to remove iron and to reveal the antigenic sites. In siderotic cerebellar cortex, ferritin reaction product occurred in the hemosiderin matrix, the cell bodies and processes of Bergmann glia, and in microglia. Astrocytes other than Bergmann glia did not contain ferritin reaction product. RCA-1 stained microglia and hemosiderin whereas antisera to alpha 1-antitrypsin and alpha 1-antichymotrypsin only reacted with iron-depleted granules. The selective vulnerability of the eighth cranial nerve was explained by the presence of ferritin-reactive and lectin-positive microglia. Hemosiderin isolated from frozen cerebellum contained ferritin, GFAP, and vimentin. The presence of the intermediate filament proteins was likely due to co-localization with hemosiderin granules in Bergmann glia. The ability of the brain to biosynthesize ferritin in response to prolonged contact with hemoglobin iron is thought to be the most important factor in the pathogenesis of superficial siderosis. The great severity of the lesion in the exposed cerebellar cortex is readily explained by accelerated ferritin biosynthesis in Bergmann glia.

Neurons of layer Vb of rat sensorimotor cortex atrophy but do not die after thoracic cord transection.

Albino rats six weeks (wk) of age underwent transection of the spinal cord at the level of the seventh thoracic vertebra. They were killed ten wk later by several schedules of formaldehyde-glutaraldehyde, formaldehyde and formaldehyde-ethanol-acetic acid perfusion-fixation. Layer Vb of the sensorimotor cortex, the site of origin of corticospinal axons severed by the operation, was searched by light and electron microscopic methods for evidence of neuronal necrosis. Cord-transected rats were compared with control, unoperated animals of identical age. Nerve cell death was not evident to qualitative study, although shrunken, deeply-staining neurons of artefactitious origin occurred capriciously in paraffin sections when fixation was initiated with a dilute formaldehyde-glutaraldehyde solution. Quantitative light and electron microscopic studies were also negative for indications of neuronal death. However, mild somal atrophy could be substantiated for layer Vb neurons of cord-transected rats by light microscopic, morphometric methods. Neuronal atrophy was unaccompanied by qualitative or quantitative ultrastructural alterations. Subcellular organelles and the per cent of neuronal plasma membrane apposed by axosomatic boutons were unchanged. Neuroglia and neuronal processes always had a normal electron microscopic appearance.

Ultrastructural features of a brain injury model in cat. I. Vascular and neuroglial changes and the prevention of astroglial swelling by a fluorenyl (aryloxy) alkanoic acid derivative (L-644,711).

We present qualitative and quantitative ultrastructural observations on the changes induced in neuroglia and blood vessels of gray matter of cat brain by an experimental acceleration-deceleration injury which, when used alone, causes negligible morbidity and mortality, but, when combined with systemic hypoxia, leads to coma and delayed death in approximately 50% of experimental subjects. An increase in the proportion of neuropil occupied by astrocytic cytoplasm is detectable qualitatively in layer Vb of pericruciate cortex 20 min after injury without hypoxia, and is maximal (22%, as measured morphometrically, vs 11.4% in controls) 40 min afterward. Near-normal values (14.1%) are obtained 100 min following the insult. If trauma is succeeded 40 min later by a 60-min period of hypoxia, there is prolongation of astrocytic edema and other neuroglial accompaniments of the traumatic lesion, such as aggregation of nuclear nucleoprotein granules and, in astrocytes, fusion of rosette ribosomes and enlargement of mitochondria. A decrease in luminal area occurs in capillaries 40 min after trauma applied alone. Hypoxia without trauma leads to a significant increase in capillary luminal area, which, however, is abolished when trauma precedes the hypoxic interlude. Intravenous injection of a non-diuretic, fluorenyl derivative (L-644,711) of (aryloxy)alkanoic acid loop diuretics, completely prevents the astrocytic swelling ordinarily present 40 min after acceleration-deceleration injury. Also, L-644,711 improves mortality and morbidity scores in cats subjected to trauma with hypoxia. We suggest that astroglial swelling may be a critical step in the evolving pathology of this head injury model and its prevention, as by L-644,711 administration, may have relevance to the treatment of cerebral edema in human head injury and other clinical disorders accompanied by astrocytic swelling.

Abnormalities of central axons in a dysmyelinative rat mutant.

The absence of normal myelin from the CNS of the dysmyelinative rat mutant, md, is associated with axonal abnormalities including organelle-poor and organelle-rich spheroids (OPS and ORS, respectively), wrinkling of the axolemma, persistence of glycogen aggregates and vacuoles in cerebellar mossy fiber terminals, and coalescence of synaptic vesicles in terminal boutons of the nucleus interpositus. OPS have a special predilection for medullary pyramid and the axons of Purkinje cells and further differ from ORS in their possession of nematosomes and in their lack of neurofilaments, microtubules, and degenerating mitochondria. Purkinje cells of md fail to increase in size after 30 days postnatal age and, unlike these neurons in normal neonatal rats, may have massed or dispersed granules of cytoplasmic glycogen which persist for at least 86 days postnatally. Morphometric study of axons of medullary pyramid and cervical corticospinal tract at 19-43 days of age shows a shift in frequency to axons of smaller size in md, as compared to age-matched controls, except that approximately 1% of md axons are larger than any encountered in controls. Finally, the pyramidal axons of md at 43 days of age have a significantly larger area of axoplasm occupied by mitochondria than obtains for the control condition. We conclude that the described abnormalities are secondary to the lack of a myelin investment and/or the loss of oligodendrocytes.

Early brain-stem auditory evoked responses in vertebrobasilar transient ischemic attacks.

Brain-stem auditory evoked response (BAER) studies were performed one to 16 days after a vertebrobasilar transient ischemic attack (VB TIA) in eight patients and repeated two to 16 days later in six of them. Initially, all showed absence of waveforms, prolonged interpeak latencies, and/or amplitude reduction. Five of six patients showed reversal of BAER changes to normal; the remaining patient returned to near normal. Normalization occurred six to 24 days after the VB TIA. These results are different from those reported in other studies. Early sequential BAER studies may be helpful in differentiating VB TIA from brain-stem infarction and syndromes that mimic VB TIA.

Muscle pathology in Bassen-Kornzweig syndrome and vitamin E deficiency.

A constellation of histologic abnormalities was demonstrated in the quadriceps femoris muscle of a 29-year-old man with Bassen-Kornzweig syndrome. The abnormalities consisted of fibers containing dense lipid inclusions ceroid and lipofuscin, a spectrum of fiber size, architectural changes, and an increase in central nuclei. A dramatic shift of fiber type predominance, from type I to type II, was demonstrated in the myosin ATPase reactions one year after vitamin E therapy. Despite an apparent reduction in the number of fibers containing lipid and ceroid granules in the second biopsy, neuromyopathic changes worsened. The relationship of these findings to vitamin E therapy is discussed.

Qualitative and quantitative ultrastructural observations on retinal ganglion cell layer of rat after intraorbital optic nerve crush.

Rat retinal ganglion cell layer (GCL) was examined ultrastructurally 1-180 days after intraorbital crushing of one optic nerve. It was confirmed quantitatively that axotomized ganglion cells lost cisternal membranes of the rough endoplasmic reticulum (RER) and showed disintegration of Nissl bodies and ribosomal rosettes 3 days postoperatively. Between 60 and 180 days after neurotomy there was partial reversion of the RER towards normal. At postoperative intervals of 14-60 days, chromatin aggregation became conspicuous and some nuclei were prominently furrowed and contained electron-dense inclusions. Concurrently, profiles of dead ganglion cells were encountered. Mean mitochondrial area increased in axotomized neurons but mitochondrial density declined, while the Golgi apparatus, lamellar specializations of the RER and the size of nuclei did not change significantly. Cytoplasmic atrophy was profound, however. Small nerve cells of the GCL appeared morphologically distinct from ganglion cells and did not undergo appreciable alteration. A decline in neuronal density, approximating 35%, occurred between the third and seventh postoperative day and progressed slowly thereafter. Neuronal density was 32% of normal 180 days postoperatively. A temporary increase in glial density 3-28 days after operation was due to microglial hyperplasia. Müller cell and astrocytic processes hypertrophied, infiltrated nerve fibre bundles, and surrounded and intruded into neuronal somata. Bundles of unmyelinated small axons, invested by astrocytes and basal lamina, were present within the necrotic cavity of the lesioned nerve 28-90 days postoperatively and had cytologic features of regenerative axonal sprouts. We conclude that intraorbital optic nerve crush is followed by a noteworthy degree of regenerative axonal sprouting which occurs and persists against a background of slow but relentless decline in the retinal ganglion cell population. This slow decline follows a rapidly-sustained loss of approximately one-third of the axotomized retinal ganglion cells during the first postoperative week. Intraorbital, as opposed to intracranial, injury of the optic nerve appears, paradoxically, to induce both a greater degree of ganglion cell death and a greater amount of regenerative axonal sprouting. Cytologic changes in axotomized retinal ganglion cells resemble those described for other populations of mammalian intrinsic neurons subjected to like injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Benign muscular dystrophy with contractures: a new syndrome?

Three patients are described with muscular dystrophy and contractures. Although this disorder bears similarities to Emery-Dreifuss disease and variants previously described, absence of cardiomyopathy is a distinguishing feature. Electrodiagnostic testing and muscle biopsy are consistent with a myopathy. An autosomal dominant pattern of inheritance is suspected, but the possibility of a Y-to-Y transmission cannot be completely excluded.