Progressive Motor Deficits Research Articles

Chronic inflammatory demyelinating polyradiculoneuropathy in diabetes mellitus

There is a higher incidence of demyelinating peripheral neuropathy responsive to immunomodulating treatment in patients with diabetes mellitus. The diagnosis is often overlooked and the patients are given the label of "diabetic neuropathy." Progressive symmetric or asymmetric motor deficit, progressive sensory neuropathy in spite of optimal diabetic control, and unusually high cerebrospinal fluid protein level in "diabetic neuropathy" should alert the clinician to the possibility of an underlying treatable demyelinating peripheral neuropathy masquerading as "diabetic neuropathy."

Quantitative measurement of neurodegeneration in an ALS–PDC model using MR microscopy

Exposure to cycad ( Cycas micronesica K.D. Hill) toxins via diet has been shown to induce neurodegeneration in vivo that mimics the progressive neurological disease, amyotrophic lateral sclerosis–parkinsonism dementia complex (ALS–PDC). In previous studies, specific cortical and subcortical cell loss was measured with conventional stained sections. In the present study, magnetic resonance (MR) microscopy was used to examine neurodegeneration in three dimensions (3D) in isolated intact brains and spinal cords. Mice were fed washed cycad for 2 months and showed progressive motor deficits resembling human ALS–PDC. CNS tissue was imaged at 17.6 T. T 2* scans were acquired on both spinal cord and brain samples with an isotropic resolution of 41 μm. Through MR volumetrics, cycad-fed mice showed significantly decreased volumes in lumbar spinal cord gray matter, substantia nigra, striatum, basal nucleus/internal capsule, and olfactory bulb. Cortical measurements of conventionally stained sections revealed that cycad-fed mice also showed decreased cortical thickness. These results show that MR microscopy (MRM) is sensitive enough to measure degeneration in this early stage model of a progressive neurological disease with strong correlations to behavioral deficits and histological results and may be applicable in vivo to the same model. Similar analysis may be used in the future as a diagnostic aid in tracking the early progression of neurological disorders in preclinical human subjects.

Extradural arachnoid cysts: a study of seven cases

Analysis of the management of 7 cases of extradural arachnoid cyst is presented. A brief review of the literature on the subject is presented. Seven cases of extradural arachnoid cysts were treated surgically between the years 1996 to 2002. These patients were analysed retrospectively. The average follow-up period was 32 months. Three patients were males and four were females and their ages ranged from 12 to 35 years. The patients presented with predominant complaint of progressive motor deficits. There were two cysts in the dorsal region, four in the dorsolumbar region and one in the cervicodorsal region. The extradural arachnoid cyst was located posterior to the dural tube and in the midline in six cases and all these cysts had bilateral multiple intervertebral foraminal extensions. In the case with a cervicodorsal cyst, the cyst was anterolateral to the dural tube and there was no foraminal extension. The surgery comprised of wide exposure of the cyst and radical marsupialization or resection of the cyst wall. There was no recurrence of the cyst during the period of follow-up. Radical resection of the walls leads to a lasting cure from extradural arachnoid cyst. The site of communication of the cyst contents with subarachnoid CSF could not be identified during the surgery in the series.

Surgical management of cervical radiculopathy.

Cervical radiculopathy presents as pain in a dermatomal distribution. Despite conservative nonoperative therapy, a large subset of patients will require surgical intervention. Indications for surgery include recalcitrant radiculopathy despite nonoperative treatment for more than 6 weeks and progressive motor deficit or disabling motor deficit (deltoid palsy, wrist drop) prior to 6 weeks. Anterior and posterior approaches have both yielded successful results in appropriately selected patients. Anterior cervical diskectomy and fusion is the generally preferred treatment for radiculopathy when there is a significant component of axial neck pain, when the disease is centrally located, or when there is any degree of segmental kyphosis. Posterior laminoforaminotomy is an acceptable choice for lateral soft disk herniations with predominant arm pain and for caudal lesions in large, short-necked individuals.

Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group.

Cytomegalovirus (CMV) has been implicated as a cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We assessed 440 infants (75 of whom were HIV-1-infected and 365 of whom were not) who had known CMV status and were born to HIV-1-infected women and who were followed prospectively. HIV-1 disease progression was defined as the presence of class C symptoms (according to the criteria of the Centers for Disease Control and Prevention [CDC]) or CD4 counts of less than 750 cells per cubic millimeter by 1 year of age and less than 500 cells per cubic millimeter by 18 months of age. At birth the frequency of CMV infection was similar in the HIV-1-infected and HIV-1-uninfected infants (4.3 percent and 4.5 percent, respectively), but the HIV-1-infected infants had a higher rate of CMV infection at six months of age (39.9 percent vs. 15.3 percent, P=0.001) and continued to have a higher rate of CMV infection through four years of age (P=0.04). By 18 months of age, the infants with both infections had higher rates of HIV-1 disease progression (70.0 percent vs. 30.4 percent, P=0.001), CDC class C symptoms or death (52.5 percent vs. 21.7 percent, P=0.008), and impaired brain growth or progressive motor deficits (35.6 percent vs. 8.7 percent, P=0.005) than infants infected only with HIV-1. In a Cox regression analysis, CMV infection was associated with an increased risk of HIV-1 disease progression (relative risk, 2.59; 95 percent confidence interval, 1.13 to 5.95). Among children infected with HIV-1 alone, but not among those infected with both viruses, children with rapid progression of HIV-1 disease had higher mean levels of HIV-1 RNA than those with slower or no progression of disease. HIV-1-infected infants who acquire CMV infection in the first 18 months of life have a significantly higher rate of disease progression and central nervous system disease than those infected with HIV-1 alone.

Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease Mutation

Transgenic mice expressing exon 1 of the human Huntington's disease (HD) gene carrying a 141-157 CAG repeat (line R6/2) develop a progressive neurological phenotype with motor symptoms resembling those seen in HD. We have characterized the motor deficits in R6/2 mice using a battery of behavioral tests selected to measure motor aspects of swimming, fore- and hindlimb coordination, balance, and sensorimotor gating [swimming tank, rotarod, raised beam, fore- and hindpaw footprinting, and acoustic startle/prepulse inhibition (PPI)]. Behavioral testing was performed on female hemizygotic R6/2 transgenic mice (n = 9) and female wild-type littermates (n = 22) between 5 and 14 weeks of age. Transgenic mice did not show an overt behavioral phenotype until around 8 weeks of age. However, as early as 5-6 weeks of age they had significant difficulty swimming, traversing the narrowest square (5 mm) raised beam, and maintaining balance on the rotarod at rotation speeds of 33-44 rpm. Furthermore, they showed significant impairment in prepulse inhibition (an impairment also seen in patients with HD). Between 8 and 15 weeks, R6/2 transgenic mice showed a progressive deterioration in performance on all of the motor tests. Thus R6/2 mice show measurable deficits in motor behavior that begin subtly and increase progressively until death. Our data support the use of R6/2 mice as a model of HD and indicate that they may be useful for evaluating therapeutic strategies for HD, particularly those aimed at reducing the severity of motor symptoms or slowing the course of the disease.

Abstracts of literature

Abstracts of literature

Neuropatía motora multifocal con bloqueo de la conducción nerviosa. Presentación de tres casos

Multifocal motor neuropathy is a severe chronic demyelinating, disimmune, crippling and potentially treatable disease. The clinical features are characterized by a syndrome of progressive motor deficiency with muscle atrophies, fasciculations, areflexia, myokimias and cramps, that sometimes we misdiagnosed as motor neuron disease. Electrophysiologically it is characterized by the occurrence of multifocal conduction blocks of motor fibres. Three patients with asymmetric multifocal motor neuropathy are reported in whom diagnosis was made by nerve conduction studies. All the patients had developed an asymmetric chronic progressive motor deficit that involved mostly upper limbs. One patient exhibited mild tactile sensory disturbances and a sural nerve biopsy showed moderated involvement of myelinated fibers. All the patients showed electrophysiologically, multifocal conduction blocks of motor fibers with spared conduction through sensory fibers at the same segments where motor conduction was blocked. The response to high doses intravenous cyclophosphamide therapy followed by 100 mg orally for six months, was satisfactory in all three patients. There was no response to previous trials with prednisone, azathioprine, and intravenous immunoglobulin. One patient was also submitted to several sessions of plasma exchange without benefit. The patient had been previously diagnosed as having motor neuron disease. The importance of early diagnosis of this disorder and the possibility of successful treatment with high doses of intravenous cyclophosphamide is stressed.

323 Characteristic of electrophysiological changes induced by cidp serum intraneural injection

Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired neuropathy, presumably of immunological origin. Its clinical presentation and course are extremely variable. CIDP is one of the few peripheral neuropathies amenable to treatment. Typical cases associate progressive or relapsing-remitting motor and sensory deficit with increased CSF protein content and electrophysiological features of demyelination. In other instances the neuropathy is predominantly or exclusively motor or sensory, CSF normal and electrophysiological studies fail to show evidence of demyelination. In such cases conventional diagnostic criteria are not filled yet the patient may respond to immunomodulatory treatments. In this paper we review the diagnostic pitfalls and clinical variants of CIDP to illustrate the problems that may arise. The different therapeutic options are reviewed. Axon loss associated with demyelination is the most important factor of disability and resistance to treatment.

Epidural anesthesia in cardiac surgery: Is there an increased risk?

Objective: To assess the risk of hemorrhagic complications associated with epidural anesthesia in patients undergoing coronary artery bypass grafting. Design: A prospective study. Setting: A cardiac surgical center associated with a university. Participants: Five hundred fifty-eight consecutive patients scheduled for coronary artery bypass surgery. Interventions: A Tuohy 18G epidural catheter was inserted the day before surgery in all patients. Measurements and Main Results: Preoperative coagulation tests, such as platelet count and prothrombin time, were performed. No patient was on oral anticoagulation therapy or had coagulation disorders. Four hundred three (72%) patients were on antiplatelet therapy, which was terminated at least 1 week before surgery. The epidural catheter was left in situ for up to 5 days. All patients were observed daily for signs of spinal cord compromise, such as radicular back pain or progressive sensory or motor deficits. There were no documented spinal hematomas. Conclusion: By following certain guidelines, the risk for the development of epidural hematoma is not increased in patients undergoing epidural anesthesia during cardiac surgery.

Microlumbar diskectomy using loupesand headlights

The surgical treatment of herniated lumbar discs using microlumbar diskectomy techniques, loupe magnification,and headlights has a well documented, highly successful, outcome. The indications for surgery include: sciatica unresponsive to nonoperative treatment; profound or progressive motor deficit interfering with function; cauda equina syndrome. A radicular pain pattern, positive tension sign, and a corroborative imaging study which is consistent with the pain complaints are important in determining the patient who may benefit from the procedure. Visualization and hemostasis are important. Positioning with the abdomen free decreases epidural venous engorgement and intraoperative bleeding. The nerve root should be clearly identified before retraction. This includes the use of magnification (eg loupes (3.5 power) and a headlight, or microscopic), adequate soft tissue and bone removal to allow identification of the root edge, and familiarity with techniques to decrease bleeding (bi-polar electrocoagulation and hemostatic agents). At the completion of the procedure, all free fragments of disk should be removed and any current stenosis addressed. The root should be free in tension and compression. It should be possible to freely pass a dural elevator anterior and posterior to the root, out the foramen. With the appropriate indications, timing and surgical technique one can anticipate a 90% to 95% clinical success rate in relieving radicular leg pain related to a herniated lumbar disk.

Datasheet at odds with government guidelines..

<h3>Abstract</h3> Mitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson’s disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety-and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD.

Successful removal of an angiographically occult arteriovenous malformation of the ventral medulla

A case with an angiographically occult arteriovenous malformation (AVM) of the ventral medulla presenting with progressive motor and sensory deficits is reported. The AVM, about 1 x 1 x 0.5 cm in size, accompanied by intramedullary haematoma, was successfully removed through a small incision placed in the right ventrolateral medulla between the vagus and the hypoglossal nerves. The patient's neurological symptoms improved after surgery.

Vascular recanalizing techniques in the hind brain circulation.

Percutaneous transluminal angioplasty (PTA) was performed in 45 patients with a manifest subclavian steal syndrome. Thirty-five of those patients were subjected to follow up examinations over a period of 6 to 18 months. Five patients suffered from severe restenosis and were treated again. Two thirds of the patients benefited from the treatment. PTA of the proximal vertebral artery was performed in 15 patients with bilateral occlusive lesions of the extracranial vertebral arteries. In 13 of these cases the neurological and the vascular states of the patients were regularly reexamined, 8 showed a marked improvement. During the 2 to 25 month observation period (average 15 months post-PTA) reocclusion was observed in only two cases. These showed no recurrent neurological sequelae. Forty-three consecutive patients with acute vertebro-basilar or basilar occlusion received intraarterial fibrinolytic therapy with streptokinase or urokinase. Twenty-three of these had presented severe deficits at the beginning of therapy (e.g. complete tetraplegia, comatous state for more than 6 hours). None of this group survived. By contrast the 20 other patients in this group presented with incomplete fluctuating or progressive motor deficits. None was comatous for more than 6 hours. Fourteen patients (33% in this group) survived. Local intraarterial fibrinolytic therapy is the only therapy successful in the treatment of progressive stroke from vertebro-basilar thrombosis.

Extensibility of the lumbar and sacral cord. Pathophysiology of the tethered spinal cord in cats.

Tethered spinal cord, or tethered cord syndrome, describes a disorder manifested by progressive motor and sensory deficit in the legs and by incontinence. Tethered cord syndrome occurs when the elongated spinal cord is anchored by a thick filum terminale or other pathological structures. The underlying mechanism is impairment of oxidative metabolism in the lumbosacral cord. The authors studied the extensibility of various parts of lumbar, sacral, and coccygeal segments in experimental animals and correlated this with the oxidative metabolism in these segments. The filum terminale possesses far greater extensibility than any spinal cord segments and functions as a buffer in preventing the cord from overstretching. The lumbar, sacral, and coccygeal segments elongate under traction only below the attachment of the lowest pair of dentate ligaments. The lower the cord segment, the greater the percentage of elongation in spite of limited elasticity of the cord tissue; this greater percentage of elongation of the spinal cord correlates with increasing impairment of the oxidative metabolism and more severe neurological deficit. These findings explain such symptoms and signs as motor and sensory deficits in the legs associated with the human tethered cord syndrome, and correspond with the high clinical incidence of incontinence. The lower spinal cord segments elongated promptly within 3 seconds after the start of traction. This implies that repeated acute hyperextension and hyperflexion, as occurs in humans, may accentuate oxidative metabolic changes that have already been caused by chronic cord tethering. The authors conclude that the elongation of the spinal cord under traction parallels the degree of metabolic dysfunction.

LAFORA'S DISEASE. DISTINCT CLINICO-PATHOLOGIC FORM OF UNVERRICHT'S SYNDROME.

<h3>Introduction</h3> THE FAMILIAL form of myoclonus epilepsy was first described by Unverricht in 1891.¹Subsequent reports have indicated that the myoclonus is merely one of the clinical features of a progressive polioencephalomyelopathy with varied pathologic findings and presumably different etiologies.^2A-2DGrand mal attacks, progressive motor deficits, amaurosis, and advancing mental deterioration are prominent features of the disorder. With anticonvulsive drugs the myoclonus and the grand mal attacks may be suppressed. Then the clinical picture is characterized by increasing dementia and motor defects quite similar to other progressive adolescent dementias. The intraneuronal inclusions of Lafora^3A,3Bhave been the dramatic neuropathologic finding. This intracellular material has been identified as belonging "to the group of acid mucopolysaccharides."⁴Similar material has been found in the heart muscle and liver cells of possibly eight cases.^4-9Such studies have indicated that Unverricht's syndrome may well be part of some as