Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study.

BACKGROUND AND PURPOSE: Deep brain stimulation of the internal globus pallidus (GPi-DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer-blinded outcome assessment of long-term GPi-DBS, with 1-year follow-up. METHODS: In this prospective, single-centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi-DBS for median (range) 30 (12-48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short-Form Health Survey-36 (SF-36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow-up. RESULTS: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19-30) to 8 (4-23) (P = 0.028), thus a 70% (23-82) score reduction. In the open evaluation, median Severity score improvement at the last follow-up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF-36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. CONCLUSIONS: This single-blinded study shows good long-term efficacy of GPi-DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.

Acute postoperative seizures after epilepsy surgery - a long-term outcome predictor?

OBJECTIVES: The prognostic value of acute postoperative seizures (APS) after epilepsy surgery is much debated. This study evaluated APS, defined as seizures in the first week post-surgery, as a predictor of long-term seizure outcome, and investigated the utility of other potential outcome predictors. MATERIALS AND METHODS: Medical records of 48 patients with temporal and extra-temporal epilepsy surgery were studied. Forty patients had lesional surgery. All had at least 2 year postoperative follow-up. RESULTS: At 2 year follow-up, 25 patients (53%) were seizure free. Univariate analysis showed that APS (P = 0.048), using ≥ six AEDs prior to surgery (P = 0.03), pathological postoperative EEG (P = 0.043) and female gender (P = 0.012) were associated with seizure recurrence. CONCLUSIONS: Univariate analysis indicate that APS, a high number of AEDs used prior to surgery, and pathological postoperative EEG are possible predictors of seizure recurrence after epilepsy surgery. Only gender retained significance in the multivariate analysis.

Is vagus nerve stimulation a treatment option for patients with drug-resistant idiopathic generalized epilepsy?

BACKGROUND: The value of vagus nerve stimulation (VNS) for treating patients with drug-resistant idiopathic generalized epilepsy (IGE) is not well documented. PATIENTS AND METHODS: Twelve patients (2 males, 10 females) with a mean age of 31 years (11-48 years) and with drug-resistant IGE had VNS implanted in the period 1995-2006. All had generalized seizures documented by video-electroencephalogram. Mean follow-up period was 23 months (9-54 months). RESULTS: There was a total seizure reduction of 61% (P = 0.0002). There was 62% reduction of generalized tonic-clonic seizures (P = 0.0020), 58% of absences (P = 0.0003) and 40% of myoclonic seizures (P = 0.0156). Eight patients were considered responders (>50% seizure reduction); two of these patients became seizure-free. Five out of seven patients with juvenile myoclonic epilepsy were responders. At the last follow-up visit, the patients had reduced the anti-epileptic drug (AED) usage from an average of 2.3 to 1.7 AED per patient (P = 0.0625). Two patients are currently being treated with VNS therapy only. Nine patients reported side effects, which were mostly mild and tended to diminish over time. CONCLUSION: Our results indicate that adjunctive VNS therapy is a favourable treatment option for patients with drug-resistant IGE. Rapid cycling seems worth trying in some of the non-responders.

Coeliac disease, unilateral occipital calcifications, and drug-resistant epilepsy: successful lesionectomy.

PURPOSE: To draw attention to the triad of coeliac disease (CD), occipital calcifications, and drug-resistant epilepsy, with focus on the outcome of epilepsy surgery. METHODS: We describe a male patient who despite a diagnosis of CD from the age of 9 did not comply with the gluten-free diet. At the age of 11 he developed simple and complex partial seizures with visual symptoms, anxiety, and ambulatory automatisms. His epilepsy appeared to be drug resistant, and after having tried nine antiepileptic drugs (AEDs), alone or in combinations, he underwent a presurgical evaluation at the age of 30. Interictal standard electroencephalograms (EEGs) disclosed frequent biparieto-occipital epileptiform discharges. Computed tomography showed cortical-subcortical punctate calcifications in the right parieto-occipital region, where his seizures seemed to start, according to ictal EEG registrations from intracranial strip electrodes. RESULTS: At the age of 31 he underwent epilepsy surgery. A 5 x 6 cm large area of the right parieto-occipital region was resected, including the area with calcifications. Except for a few short-lasting episodes of anxiety (simple partial seizures?) he has now been seizure-free for 12 years. AEDs were withdrawn 5 years ago. Postoperatively he was left with an upper left-sided quadrant anopsia, which is not bothering him. CONCLUSIONS: In patients with CD, unilateral occipital calcifications, and drug-resistant epilepsy, epilepsy surgery should be considered, as a lesionectomy might be very successful.

Emotional responses during unilateral amobarbital anesthesia: differential hemispheric contributions?

OBJECTIVES: To explore (1) effects of test and subject variables in determining euphoric and dysphoric responses during unilateral amobarbital anesthesia and (2) which cerebral areas contribute to the emotional responses. METHOD: Incidence of euphoric and dysphoric reactions during left- and right-sided amobarbital anesthesia of the internal carotid artery (ICA) and selective anesthesia of the middle cerebral (MCA) and the posterior cerebral (PCA) artery was recorded. The sample comprised 270 Norwegians (6-61 years), and a total of 562 injections were performed under conditions endeavoring to calm down the patients. RESULTS: The overall incidence of observed emotional responses during ICA anesthesia was 21.5%, euphoric reactions being about 10 times more frequent than dysphoric. The incidence of euphoric reactions, however, was not significantly higher under right- than under left-sided anesthesia, and dysphoric reactions were not more frequent under left- than under right-sided anesthesia. Indeed, 13 patients showed elevated mood under both right- and left-sided anesthesia. Anesthesia of the territories of ICA and MCA gave rise to similar results, while no cases of mood change were observed under selective PCA anesthesia. CONCLUSION: It is concluded that unilateral amobarbital anesthesia as such, irrespective of side, may trigger both euphoric and dysphoric responses. The relative frequency obtained is influenced importantly both by the emotional responsiveness of the subjects and the emotional climate of the test situation. Finally, it is suggested that brain regions supplied by the PCA contribute less to modulation of euphoric and dysphoric responses than those supplied by the MCA or the ICA.

[Chronic intermittent vagal nerve stimulation--a new therapeutic approach in epilepsy]. / Kronisk intermitterende stimulering av nervus vagus--en ny behandlingsform ved epilepsi.

BACKGROUND: Vagal nerve stimulation is a new non-pharmacological therapy for patients with refractory epilepsy. Introduced in USA in 1988, the treatment is based on animal experiments demonstrating that intermittent stimulation of the vagal nerve could prevent or reduce the frequency and/or duration of seizures. MATERIAL AND METHODS: At the National Hospital in Norway, 47 therapy-resistant patients have had a vagal nerve stimulator implanted since June 1993. We have used the Neuro-Cybernetic Prosthesis system from Cyberonics, consisting of a programmable pulse generator, a bipolar vagal nerve stimulator lead, a programming wand with accompanying software, and a hand-held magnet. The mean age of the population was 34.4 years (12-70 years). All had a long-standing epilepsy with frequent seizures, 36 (77%) had seizures every day. The majority (89%) had localization-related epilepsy. Mean follow-up time was 2.7 years (0.4-6.5 years). RESULTS: 16 patients (34%) responded to the treatment with > 50% reduction in seizure frequency. No one, however, became seizure free. 20 patients (43%) had no seizure reduction. 24 of the patients (51%) benefited from extra stimulation triggered by the magnet. The stimulation affected several types of seizures; most often a reduction in frequency of secondary generalised tonic-clonic seizures was noted. Hoarseness, coughing and a tingling sensation in the throat were the most frequently reported side effects occurring during stimulation. The patients tended to habituate to these side effects. In 14 patients (30%), the device has been explanted, mostly due to lack of efficacy. INTERPRETATION: Considering the fact that this patient group belongs to the most refractory part of the epilepsy population, the results are regarded as promising and they are in keeping with results from other studies. However, the role of vagal nerve stimulation in the future treatment of epilepsy is still not settled. Several questions remain unanswered, e.g. what are the exact mechanisms of action behind the seizure reducing effect, and which patients are most suitable for this treatment?

Measured increase in intracellular Ca(2+) during stimulated release of endogenous glutamate from human cerebrocortical synaptosomes.

Presynaptic terminals (synaptosomes) prepared from guinea pig and rat cerebral cortex release endogenous glutamate in a Ca(2+)-dependent manner in response to membrane depolarisation. In the present study, synaptosomes were prepared from human cerebral cortex removed in association with temporal lobe resections in epileptic patients. The cytosolic free Ca(2+) concentration increased from 474+/-66 before to 649+/-89 nM after 2 min depolarisation. The basal level of free cytosolic Ca(2+) is higher and the increase in response to depolarisation is more pronounced in human synaptosomes than observed in animal experiments. The Ca(2+)-dependent glutamate release, estimated as the difference between total - and the Ca(2+)-independent glutamate release, increased from 0 to 5.4+/-1.9 nmol/mg protein. The released amount of glutamate is larger than reported in animal models. These results demonstrate that membrane depolarisation of synaptosomes from human brain evokes a rapid rise in cytosolic free Ca(2+) and a more prolonged rise in synaptic, Ca(2+)-dependent glutamate release.

[Life-saving hemicraniectomy in acute massive brain infarction]. / Livreddende hemikraniektomi ved akutt massivt hjerneinfarkt.

Acute occlusion of the middle cerebral artery is an important cause of ischemic stroke. The resulting brain infarction is often very large, leading to massive brain oedema and intracranial hypertension. Despite intensive medical treatment, the mortality rate due to herniation and cerebral circulatory arrest remains very high. A Norwegian left-handed male, 28 years of age, developed signs of impending herniation following an acute right-side middle cerebral artery occlusion. When admitted to neurosurgical care 54 hours after the stroke, he was soporous, had a left-side hemiparalysis, conjugated deviation of the gaze and a mydriatic pupil on the right side. The intracranial pressure level was between 30 and 40 mm Hg. Following a right-side hemicraniectomy, the intracranial pressure fell to levels around 20 mm Hg. The bone flap was replaced four months later. One year after the stroke, the patient is fully independent of others, despite a left-side hemianopia and hemiparesis. Hemicraniectomy may be indicated in selected patients with impending herniation due to brain infarction. Intracranial pressure recordings are useful as an adjunct in the management of these patients. Our report seems to be the first account of decompressive hemicraniectomy performed in Norway for acute massive brain infarction.

[Continuous intrathecal infusion of baclofen. A new therapeutic method for spasticity]. / Kontinuerlig intratekal infusjon med baklofen. Ny behandlingsmetode for spastisitet.

Intrathecal administration of baclofen is now generally accepted as a powerful treatment of spasticity caused by spinal lesions. 35 patients with severe spasticity, 29 of spinal origin and six of supraspinal origin resistant to conservative treatment, had a programmable pump (Synchromed, Medtronic) for continuous intrathecal baclofen infusion implanted. The patients were followed-up for an average of 29 months (0-68). The initial effect of the treatment was positive for all patients; spasms were less frequent, there was remission of pain caused by cramps, and in some cases improved ambulation. In five patients, however, the pump was later removed: in two patients the pump ceased to be effective, two patients became infected, and one experienced multiple catheter problems. Problems with the catheter was the most common complication experienced, and this was seen in nine patients. Three patients died of the underlying disease. The majority of patients became accommodated to intrathecal baclofen and it was necessary to administer increasingly larger doses to maintain the clinical effect. Long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients, but close follow-up is necessary for assessing efficacy and refilling the pump.

Hypothalamocerebellar and cerebellohypothalamic projections--circuits for regulating nonsomatic cerebellar activity?

Cerebellar involvement in visceral and affective responses is known from physiological and behavioral studies, but the pathways involved in these responses have remained enigmatic. Over the last ten years neuroanatomical studies have shown that the cerebellum and hypothalamus are interconnected by direct hypothalamocerebellar and cerebellohypothalamic projections and by a multitude of indirect pathways. The hypothalamocerebellar projection terminates in the cerebellar nuclei and in all layers of the cerebellar cortex as multilayered fibres. This projection is, at least in part, histaminergic. New immunocytochemical experiments indicate that small numbers of hypothalamocerebellar neurones may contain GABA- or glycine-like immunoreactivity. GABA may function as a transmitter in hypothalamocerebellar fibres, probably in conjunction with histamine, but it is not clear whether glycine may also function as a transmitter or only serve metabolic functions. The bidirectional pathways between the cerebellum and hypothalamus may be part of the circuits through which the cerebellum participates in the modulation of a variety of nonsomatic events. In addition, new observations on patients with well localized cerebellar lesions reveal simultaneous somatic and visceral dysfunction. Recent research on direct hypothalamocerebellar pathways and on other connections between hypothalamus and cerebellum is reviewed. It is hypothesized that the cerebellum may act as a general modulator and coordinator of a wide range of central nervous activities, somatic as well as nonsomatic.

The hypothalamocerebellar projection in the cat: branching and nuclear termination.

The hypothalamic projection to the cerebellar nuclei and cortex in the cat was studied by means of retrograde transport of wheat germ agglutinin-horseradish peroxidase complex and various fluorescent tracers. The hypothalamocerebellar nuclear projection originates from various parts of the posterior hypothalamus and reaches mainly the ipsilateral fastigial and interposed nuclei, but all nuclei receive some hypothalamocerebellar fibres. It appears from our double labelling experiments that at least one half of the hypothalamocerebellar nuclear neurones by means of axon collaterals also projects to the cerebellar cortex. Experiments with depositions of fluorescent tracers in both cerebellar hemispheres show that some hypothalamocerebellar fibres branch to reach different parts of the cerebellar cortex. Previous studies have shown that hypothalamocerebellar axons may be branches of hypothalamic efferents to other sites. However, experiments with combined fluorescent tracer depositions in the cerebellum and hippocampus gave no evidence for hypothalamic neurones with axon collaterals to both these regions.

Separate populations of neurons in the oculomotor nucleus project to the cerebellum and the abducent nucleus. A retrograde fluorescent double-labelling study in the cat.

Retrograde transport of fluorescent substances was used in order to investigate possible branching of axons from neurons in the oculomotor nucleus in the cat. Rhodamine-B-isothiocyanate (RITC) was injected into the cerebellar hemisphere, while Fluoro-Gold was implanted into the abducent nucleus. Neurons single-labelled with either of the dyes were found in the oculomotor nucleus in all cases, but no double-labelled neurons were found. The labelled cells were smaller than motoneurons and located in partly overlapping areas along the dorsal border of the oculomotor nucleus, with the RITC labelled cerebellar projecting cells concentrated medially and the Fluoro-Gold labelled neurons projecting to the abducent nucleus concentrated laterally. The RITC labelled cells were found throughout the rostrocaudal extent of the nucleus, while the Fluoro-Gold labelled cells were mainly found caudally. The present findings demonstrate that oculomotor neurons projecting to the feline cerebellum and abducent nucleus represent separate cell populations.

Non-motoneurons in the facial and motor trigeminal nuclei projecting to the cerebellar flocculus in the cat. A fluorescent double-labelling and WGA-HRP study.

The cerebellar projection from the facial and motor trigeminal nuclei was studied in the cat by means of retrograde axonal transport of wheat germ agglutinin-horseradish peroxidase and fluorescent tracers. The feline facial nucleus was cytoarchitectonically subdivided into ventromedial, ventrolateral, lateral, dorsal, intermediate and medial divisions (see Papez 1927), and the motor trigeminal nucleus into medial, ventral, intermediate, lateral and dorsal divisions. The neurons in the facial and motor trigeminal nuclei were classified as small (ovoid to round cells with a maximum diameter of the cell body of about 20 microns) or large (polygonal to round cells with maximum diameter of about 40 microns). After floccular injections of the wheat germ agglutinin-horseradish peroxidase complex, retrogradely labelled cells were found throughout the facial nucleus, but especially in its medial and dorsal divisions. In the motor trigeminal nucleus, labelled neurons were found only in the ventral, intermediate and lateral divisions. Cases with tracer deposition (implants or injections) in other parts of the cerebellar cortex or nuclei were all negative. All facial and motor trigeminal neurons labelled after floccular injections were smaller than the neurons labelled after injections in the facial mimic and masticatory muscles, and only single-labelled neurons were found following floccular injections of Fluoro-Gold and muscular injections of rhodamine-B-isothiocyanate in the same animals. These observations strongly suggest that the neurons in the facial and motor trigeminal nuclei which project to flocculus are of the non-motoneuron type.

Observations on the projection from the perihypoglossal nuclei to the cerebellar cortex and nuclei in the cat. A retrograde WGA-HRP and fluorescent tracer study.

The origin and distribution of cerebellar cortical and nuclear afferents from the perihypoglossal nuclei have been studied by means of retrograde transport after implants and injections of the wheat germ agglutinin-horseradish peroxidase complex in the cat. The projection reaches all the cerebellar nuclei as well as vermal, intermediate and lateral parts of the cerebellar cortex. It is bilateral with an ipsilateral predominance and originates from all the perihypoglossal nuclei. The majority of the projecting neurons are situated caudally in the nucleus prepositus, while smaller numbers of projecting neurons are located in the rostral part of this nucleus, in the rostral nucleus intercalatus and in the nucleus of Roller. Small and medium-sized spindle-shaped to round cells located throughout the nucleus prepositus and in the rostral nucleus intercalatus have widespread projections, reaching all parts of the cerebellar cortex and nuclei, whereas large multipolar cells located in the caudal ventromedial part of the nucleus prepositus and in the nucleus of Roller have projections only to the flocculus and nodulus and the lateral and intermediate cortices. Retrograde fluorescent double-labelling experiments were made to investigate possible axonal branching of the perihypoglosso-cerebellar fibres. In experiments with injections of rhodamine-B-isothiocyanate (RITC) in the left cerebellar hemisphere and implants of crystalline Fluoro-Gold in the right hemisphere, single- and double-labelled cells were found intermingled throughout the perihypoglossal nuclei. Experiments with cerebellar cortical injections of RITC and implants of crystalline Fluoro-Gold in the underlying nucleus, demonstrated single- and double-labelled cells in the nucleus prepositus and the rostral nucleus intercalatus, while only single-labelled RITC neurons were seen in the group of large neurons in the ventromedial part of the nucleus prepositus and the nucleus of Roller. After injections of RITC in the cerebellar cortex and implants of crystalline Fluoro-Gold in the abducent nucleus on the same side, double-labelled neurons were found only in the rostral nucleus prepositus.

Demonstration of a sparse direct projection from the interstitial nucleus of Cajal to the cerebellum in the cat.

In the cat the possible contribution of cerebellar afferents from the accessory oculomotor nuclei was investigated by means of retrograde transport of the wheat germ agglutinin-horseradish peroxidase complex. A sparse bilateral projection from the interstitial nucleus of Cajal was demonstrated. The fibres reach cerebellar cortical as well as nuclear regions. No retrogradely labelled cells were found in the nucleus of Darkschewitsch and the nucleus of the posterior commissure.

Cerebellar cortical and nuclear afferents from the Edinger-Westphal nucleus in the cat.

The cerebellar projection from the Edinger-Westphal nucleus was studied in the cat by means of retrograde transport of the wheat germ agglutinin-horseradish peroxidase complex. The present findings give evidence that the flocculus is the main terminal area. However, small tracer implants and injections into various parts of the cerebellar nuclei and cortex revealed projections also to the fastigial and interposed nuclei and to most parts of the anterior and posterior lobe cortices. The projecting neurons are small and located bilaterally throughout the Edinger-Westphal nucleus. No topical differences between the projections to different parts of the cerebellum were found.

The feline oculomotor nucleus: morphological subdivisions and projection to the cerebellar cortex and nuclei.

The cytoarchitecture of the feline oculomotor nucleus was examined in sections stained with thionin and neutral red. Five different subdivisions (caudal central, paramedian, ventral, dorsomedial and dorsolateral divisions) can be identified on each side of the midline. This observation is discussed, and our findings are compared to previous studies of the cytoarchitecture or central muscular representation of the oculomotor nucleus in which different subgroups have been distinguished. Implants or injections of the wheat germ agglutinin-horseradish peroxidase complex have revealed that all five subdivisions project to different parts of the cerebellar cortex and nuclei. Retrogradely labelled cells were found in the oculomotor nucleus in 18 cases following deposition of tracer in the fastigial and interposed nuclei and certain regions of the anterior, posterior and flocculonodular lobes. The projection is bilateral and appears to have its main termination in flocculus. It originates from small neurons, especially from those located along the dorsal border of the oculomotor nucleus.