Electricity in the treatment of nervous system disease.

Electricity has been used in medicine for almost two millenniums beginning with electrical chocks from the torpedo fish and ending with the implantation of neuromodulators and neuroprostheses. These implantable stimulators aim to improve functional independence and quality of life in various groups of disabled people. New indications for neuromodulation are still evolving and the field is rapidly advancing. Thanks to modern science and computer technology, electrotherapy has reached a degree of sophistication where it can be applied relatively safely and effectively in a variety of nervous system diseases, including pain, movement disorders, epilepsy, Tourette syndrome, psychiatric disease, addiction, coma, urinary incontinence, impotence, infertility, respiratory paralysis, tinnitus and blindness.

CARD15/NOD2 gene variants are associated with familially occurring and complicated forms of Crohn's disease.

BACKGROUND: Variants of the caspase activating recruitment domain 15/nucleotide oligomerisation domain 2 (CARD15/NOD2) gene have been associated with susceptibility to Crohn's disease (CD). AIM: Our aim was to evaluate the allele frequencies of the CARD15 variants R702W, G908R, and 1007fs in Finnish inflammatory bowel disease (IBD) patients and to search for possible associations between CARD15 variants and occurrence of familial forms of IBD or complicated forms of CD. PATIENTS AND METHODS: We investigated 198 sporadic CD patients, 46 probands with familial CD, 27 CD probands from mixed IBD families, 99 unrelated patients with ulcerative colitis (UC), and 300 control individuals for the occurrence of the CARD15 gene variants R702W, G908R, and 1007fs. RESULTS: In CD patients, the allele frequencies for the rare variants of these polymorphisms were 3.3%, 0.6%, and 4.8% (total 8.7%), and the corresponding frequencies in healthy controls were 1.8%, 0%, and 1.7% (total 3.5%) (8.7% v 3.5%; p<0.01). In UC patients allele frequencies were comparable with those in controls. The frequency of the 1007fs polymorphism variant allele was significantly higher among all CD patients than in controls (4.8% v 1.7%; p<0.01) but there was no significant difference in allele frequencies between the CD and UC groups. The 1007fs allele frequency was higher in familial CD than in non-familial cases with CD (10.9% v 3.5%; p<0.01). There were no significant differences in the allele frequencies of the R702W and G908R polymorphisms between CD patients, UC patients, and controls. We found that 15.5% of CD patients, 9.1% of UC patients, and 6.7% of controls carried at least one of the CARD15 variants. In CD patients carrying at least one of the three NOD2 variants, the ileum was affected more often than in non-carrier CD patients (90% v 73%; p<0.05), they had stricturing or penetrating disease more often than non-carriers (88% v 56%; p<0.01), and they had an increased need for bowel surgery. CONCLUSIONS: The frequency of NOD2 gene variants was lower in genetically homogenous Finns than in other populations. The 1007fs variant was associated with CD. The occurrence of CARD15 variants predicted ileal location as well as stricturing and penetrating forms of CD.

The neuron theory.

In 1740 the Swedish scientist and philosopher Emmanuel Swedenborg described what is the first known anticipation of the neuron (a nerve cell with its processes). One hundred years later Ehrenberg, Remak and Purkinje recognized the nerve cell as the important element of the nervous system and provided its first accurate description. Vilhelm von Waldeyer in 1891 proposed to call the unit 'neuron' from the Greek word for 'sinew'. The 'neuron theory' or 'neuron doctrine', which emerged at the end of the 19th century, asserts that nerve tissue is composed of individual cells, which are genetic, anatomic, functional and trophic units. The pioneers of the neuron doctrine included neuroscientists, physicians, a polar explorer and three Nobel Laureates. The classic neuron doctrine has served well as the theoretical basis for the great advances in our current understanding of the cellular basis of nervous system functions.

The neuron doctrine, the mind, and the arctic.

The late 19th century and early 20th century represent an era of significant progress and important discoveries. Explorers of unknown continents interacted with pioneers of neuroscience, including the founders of the neuron doctrine, which asserted that nerve tissue was composed of individual cells that were genetic, anatomic, functional, and trophic units. Fridtiof Nansen (1861-1930), an arctic explorer and a cofounder of the neuron doctrine, knew Sigmund Freud (1856-1939), a neuroscientist and the founder of psychoanalysis, as well as Harvey Cushing (1869-1939), the father of modern neurosurgery. This is an account of the evolution of the neuron doctrine at a time of great explorers and scientists, with insight into their common interests and interactions on scientific and social levels.

Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects.

Analysis of the entire coding region of the HERG gene of 39 Finnish LQTS patients revealed eight mutations, six of which are hitherto unreported. All these mutations are located in the evolutionarily conserved regions of HERG, including the transmembrane domains (P451L, Y569H, 1631delAG, G584S, G601S, T613M) and the cytoplasmic N-terminus (453delC, R176W) of the channel. Our present and earlier results suggest that the LQT2 subtype accounts for approximately 20-30% of LQTS cases in Finland. We also report the first common amino acid polymorphism (K897T) of the HERG channel, with allele frequencies of 0.84 and 0.16. Investigation of 170 genetically homogenous LQT1 patients suggests that this polymorphism may influence QT interval in female individuals.

Arctic and Antarctic exploration including the contributions of physicians and effects of disease in the polar regions.

A history of Arctic and Antarctic exploration, whether to find a Northwest Passage, North Pole, or South Pole, is a story of triumph and tribulation. The hardship experienced by polar explorers in the last 1000 years permeates the tales of achievement. Physicians and surgeons have played prominent roles in all major polar explorations. No significant Arctic voyage, particularly in the last 300 years, was made without a member of the party trained in the management of medical emergencies and in basic surgery. During times of health, surgeons functioned as the voyage naturalists with expertise in biology, botany, zoology, and the writing of scientific catalogs. Spurred by our interest and fascination with the history of polar exploration, we reviewed the roles of physicians and natural scientists in Arctic and Antarctic adventures.

Do microelectrode techniques increase accuracy or decrease risks in pallidotomy and deep brain stimulation? A critical review of the literature.

Several recent publications have stated that the use of microelectrode recording (MER) during pallidotomy or deep brain stimulation (DBS) contributes to decreasing risks and side effects of surgery, and that such a technique is a prerequisite for minimizing lesion size and for accurate placement of the stereotactic lesion or the DBS electrode. To evaluate the consistency of these statements, we reviewed hundreds of papers and congress reports on MER- and non-MER-guided procedures published since 1992. This review showed that MER groups published more often than non-MER groups. While side effects of surgery were not uncommon in both groups, the rate of severe complications, such as hematoma, and mortality appeared to be higher when microelectrodes were used, both in ablative surgery and in DBS procedures. Besides, the nonaccurate placement of lesions or DBS electrodes, as assessed on published MRI figures, was not uncommon in MER publications. Lesion volume was, when reported, not different in both techniques. The electrical parameters of stimulation of implanted electrodes in the thalamic ventral intermediate (Vim) nucleus for treatment of tremor were higher in MER-guided surgery. The available literature suggests that MER techniques may increase the risks of surgery without enhancing its accuracy, compared to MRI-based macrostimulation techniques. To date, there is no randomized trial by one and the same group on the use of micro- versus macroelectrodes in surgery for movement disorders. A prerequisite for such a trial in the future must imply that the investigators have an equal nonprejudiced attitude towards, and equal confidence and experience in, either technique. Since such a prerequisite does not exist so far in the functional stereotactic community, a critical and comparative study of the available literature remains the only way to evaluate the pros and cons of either technique, in terms of targeting accuracy and surgical complications.

Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor.

Fifty-eight patients, 36 with essential tremor (ET) and 22 with Parkinson's disease (PD), received deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) nucleus. The mean follow-up was 17 months for ET and 21 months for PD patients. Stimulation parameters were adjusted as needed, at various intervals after surgery. Results were assessed using routine clinical evaluation and established outcome scales. All patients needed incremental increase in stimulation parameters at various intervals during the first 6-12 months after surgery. The mean voltage 1 week postoperatively was 1. 45 V in PD patients, and 1.37 V in ET patients. Twelve months later, the figures were 2.14 V in PD and 2.25 V in ET patients. At 1 year, the Essential Tremor Rating Scale (ETRS) improved from 54 to 28 (p < 0.0001). The motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) improved from 37 to 26 (p < 0.01). Tremor items of the UPDRS improved more markedly (p < 0.0001). One week postoperatively 90% of PD, and 89% of ET patients were tremor free. One year later, 70% of PD and 60% of ET patients remained mostly tremor free. Upon switching off stimulation, there was a clear tendency for tremor rebound (p = 0.07) in the PD group, requiring continuous 24-hour stimulation in some patients. Permanent non-adjustable ataxia was induced by stimulation in 2 PD patients.

Moyamoya disease in patients of Finno-Ugric origin.

The terms moyamoya disease, moyamoya syndrome and moyamoya phenomenon can be found dispersed throughout the literature. The diagnostic criteria for moyamoya disease are: (1) stenosis or occlusion of the anterior cerebral, middle cerebral and internal carotid arteries, (2) an abnormal vascular network near these arteries and (3) bilateral findings. When only the two first conditions are present, the term moyamoya syndrome is used. The incidence of moyamoya disease is high in the Mongol race, although the moyamoya syndrome is more frequently reported among Caucasians. In the last two decades 41 cases of moyamoya were diagnosed in two Hungarian and two Scandinavian hospitals, respectively. Thirty-one patients were operated on 12 unilaterally and 19 bilaterally--either with extracranial/intracranial bypass (29 cases) or with encephalomyosynangiosis (2 cases). After a mean follow-up of seven years, 67.7% of the operated cases were symptom-free or neurologically improved. The majority of the patients had moyamoya disease and turned out to be of Finno-Ugric or Lapplandish ancestry. These people originally migrated from the East and belong to the Ural-Altaic family. Our findings suggest that while the moyamoya syndrome is found in different races, the moyamoya disease may be limited to people of Eastern (Mongol) origin. Revascularization surgery may be of benefit to patients with moyamoya.

CT assessment of subarachnoid haemorrhage. A comparison between different CT methods of grading subarachnoid haemorrhage.

A number of different CT classifications of subarachnoid haemorrhage (SAH) were applied to a consecutive series of 50 patients with aneurysmal SAH. The best correlation with delayed ischaemic deficits (DID) was obtained with a score formed by the sum of the individual cisternal grades except that of the cortical subarachnoid space. The findings emphasize the significance of the extent of the SAH, rather than the presence of a localized cisternal clot with regard to the development of DID.

Subarachnoid blood on CT and memory dysfunctions in aneurysmal subarachnoid hemorrhage.

Ninety patients with a previous subarachnoid haemorrhage (SAH) were given a set of memory tests comprising immediate free recall of words (indexing long-term memory, LTM, and short-term memory, STM), final free recall of words (indexing LTM), final cued recall of words (indexing LTM), and a digit span test (indexing working memory, WM). Patients with a large amount of blood on CT, carried out within 72 h of the bleed, showed LTM as well as STM dysfunction, whereas patients with a small amount of subarachnoid blood evidenced only STM dysfunction. Patients with the ruptured aneurysm located on the anterior cerebral artery, however, constituted an exception with dysfunction of both LTM and STM together with intact WM, independent of the amount of subarachnoid blood. Also, patients with internal carotid artery or middle cerebral artery aneurysms and large volume SAH displayed LTM dysfunction, but differed concerning STM, the former showing intact STM and the latter showing STM dysfunction. Thus, it appears, that the combined information from factors such as the amount of subarachnoid blood and the location of the ruptured aneurysm is of vital importance for explaining the different patterns of memory dysfunctions after SAH.

Intractable singultus: a diagnostic and therapeutic challenge.

Hiccup or singultus is a repeated involuntary, spasmodic contraction of the diaphragm accompanied by a sudden closure of the glottis mediated by sensory branches of the phrenic and vagus nerves as well as dorsal sympathetic afferents. The principle efferent limb and diaphragmatic spasms are mediated by motor fibers of the phrenic nerve. Hiccup has been classified as a respiratory reflex and the central connection probably consists an interaction among the brainstem respiratory centers, phrenic nerve nuclei, medullary reticular formation and the hypothalamus. Chronic intractable hiccup may be due to brainstem seizures, and baclofen may be the long-awaited remedy for intractable hiccup as demonstrated in three illustrative cases.