Role of Atlantoaxial and Subaxial Spinal Instability in Pathogenesis of Spinal "Degeneration"-Related Cervical Kyphosis.

BACKGROUNDS: The role of subaxial and atlantoaxial instability in the pathogenesis of "degeneration"-related cervical kyphosis is evaluated. MATERIAL AND METHODS: During the period 2013-2016, the authors treated 21 patients having cervical kyphosis that was related to degenerative spinal disease. The patients presented with symptoms related to cervical myelopathy. Kyphosis was diagnosed on the basis of described radiologic parameters. The patients were divided into 3 groups. Group A (10 patients) had manifest radiologic evidence of atlantoaxial dislocation, type 1 facetal instability, abnormal increase in atlantodental interval, and evidence of cord compression by the odontoid process. Group B (5 patients) had axial or central atlantoaxial facetal instability (type 2 or 3 atlantoaxial facetal instability) and subaxial spinal instability. Group C (6 patients) had subaxial spinal instability. The patients were treated by only stabilization. Group A patients underwent atlantoaxial fixation, group B patients underwent atlantoaxial and subaxial fixation, and group C patients underwent only subaxial spinal fixation. The operation was aimed at arthrodesis of the spinal segments. No bone or soft tissue decompression was done. RESULTS: During the minimum follow-up period of 6 months, all patients improved in their neurologic symptoms and demonstrated evidence of spinal arthrodesis. There were no major surgical complications. CONCLUSIONS: Spinal instability plays a major role in the generation of cervical spinal kyphosis. Atlantoaxial instability may form the primary and nodal site of development of the process of spinal degeneration in general and kyphosis in particular.

Mesial temporal lobe epilepsy in a patient with spinocerebellar ataxia type 13 (SCA13).

We report a female patient of German descent with a molecular diagnosis of SCA13 who presented with a history of cerebellar ataxia and epilepsy. The underlying mutation R420H had been shown to cause a dominant negative effect on the functional properties of the voltage-gated potassium channel KCNC3. Despite widespread KCNC3 expression in the central nervous system, the patient presented with a left mesiotemporal electroencephalogram focus and left hippocampal sclerosis. This is the first case, which reports an association between mesial temporal lobe epilepsy and spinocerebellar ataxia type 13. This demonstrates that epilepsy of structural-metabolic cause may be contingent upon genetically defined channelopathies.

Neuroprotective effects of mesenchymal stem cell transplantation in animal model of cerebellar degeneration.

BACKGROUND: The cerebellum has been considered a key structure for the processes involved in sensorimotor integration ultimately leading to motor planning and execution of coordinated movement. Thus, motor deficits and behavioral changes can be associated with cerebellar degeneration. METHODS: Here, the chemical neurotoxin pyridine-2,3-dicarboxylic acid (quinolinic acid, QA) used to create partially cerebellar degeneration in adult Wistar rats suitable for use in stem cell transplantation studies. Stereotaxicaly administration of QA (0.2 mmol) in the right cerebellar hemisphere (folia VI) caused noticeable motor disturbance in all treated animals. Forty-eights hours after causing lesion, rat bone marrow-derived mesenchymal stem cells (MSCs) were transplanted into damaged cerebellar hemisphere. We investigated the role of MSC transplantation in forms of motor and non-motor learning that involves the cerebellum and its neuroprotective effects in Purkinje cells loss. RESULTS: CM-Dil labeling showed that the transplanted MSCs survived and migrated in the cerebellum 6 weeks after transplantation. The MSC-transplanted group showed markedly improved functional performance on the rotating rod test (P≤0.0001) and beam walking test (P≤0.0001) during 6 weeks compared with the controls. For non-motor learning, we used passive avoidance learning test in 3 weeks after transplantation. The results showed that MSC transplantation prevented the development of memory deficit caused by cerebellar degeneration (P≤0.001). Stereological analysis in 6 weeks after transplantation showed that QA significantly decreases Purkinje cells in vehicle-treated rats and MSC transplantation is neuroprotective and decreases Purkinje cell loss in MSC-treated rats (P≤0.0001). CONCLUSION: The results indicate that transplantation of MSCs can significantly reduce the behavioral and neuroanatomical abnormalities of these animals during 6 weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow-derived adult stem cells promises for treatment of cerebellar diseases.

Transforaminal lumbar interbody fusion (TLIF) and unilateral transpedicular fixation.

TLIF (transforaminal lumbar interbody fusion) is a method of interbody fusion, which is alternative to other vertebral fusion wherein, with an approach through intervertebral foramen, through lateral segment of intervertebral space, complications occurring with other methods are reduced. Today, there are numerous versions of this method in terms of implants and transplants. At our Department patients with axial pain resistant to conservative treatment of minimum six months underwent TLIF method with unilateral transpendicular fixation with polyaxial screws, CAGE filled with autologous transplant obtained by lamina resection, and posteromedial contralateral fusion. 22 procedures were performed at 22 levels, 10 for relapsing hernia, and 12 for disc herniation combined with degenerative changes on the same level. Pain reduction was significant; according to VAS score, lumbar pain was reduced from preoperative 8.5 +/- 0.8 to 2.4 +/- 0.85 (-72.63%) a year after, and leg pain was reduced significantly from preoperative 8.45 +/- 0.91 to 2.072 +/- 0.81 (71%) 12 months after surgery. The Wilcoxon paired test demonstrated a significant difference between preoperative VAS score and the value measured 12 months after surgery (n = 22, Z = 4.1, p < 0.001) leg and back, respectively. In 15 (68.2%) patients fusion was evidenced on standard X-ray of lumbar spine, and in 4 patients, with aggravated clinical presentation, fusion in 2 patients and pseudoarthrosis in 2 patients were evidenced by CT. Total 17 patients (77.3%) showed signs of fusion. In our study we demonstrated that unilateral ipsilateral transpedicular fixation, with positioning of one CAGE filled with local autologous transplant represents a reliable and successful method of treatment of axial lumbar pain.

Influence of repetitive transcranial magnetic stimulation on disease severity and oxidative stress markers in the cerebrospinal fluid of patients with spinocerebellar degeneration.

Ataxia severity, cerebellar hemispheric blood flow (CHBF), ascorbate free radical (AFR), superoxide dismutase protein, superoxide scavenging activity, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in cerebrospinal fluid (CSF) were compared before and after an 8-week course of repetitive transcranial magnetic stimulation (rTMS) in 20 patients with spinocerebellar degenerations (SCD). SCD patients showed higher AFR, 8-OHdG, and superoxide scavenging activity than 19 controls. In SCD patients, AFR and ataxia severity declined, and CHBF increased after rTMS. As the SCD patients showed negative correlations between ataxia severity and CHBF or superoxide scavenging activity, the therapeutic mechanism of rTMS may involve decreased oxidative stress and increased CHBF.

Olivopontocerebellar atrophy presenting with stridor.

The spectrum of degenerative ataxia includes the symptomatic degenerative ataxias and the primary degenerative ataxias. The later may be sporadic and idiopathic or hereditary, being genetically determined. When an individual ataxic patient presents with an adult-onset degenerative ataxia and has a negative family history, the physician is faced with a diagnosis of pure idiopathic sporadic degenerative ataxia or one of the hereditary ataxias. The clinical spectrum of olivopontocerebellar atrophy (OPCA) usually consists of pancerebellar signs with pyramidal and abnormal eye movements. Although Stridor is more commonly found in multisystem atrophy, it is rarely seen in OPCA. We, here report a case of third decade onset of ataxia presenting with stridor.

Orthopedic management in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

OBJECTIVE: To review the orthopedic management of choice in patients having autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). DESIGN: A retrospective study from April 1978 to April 1997. SETTING: Centre hospitalier de la Sagamie, Chicoutimi, Que. PATIENTS: A review of the records of patients having ARSACS who were identified in the registry of the Neuromuscular Diseases Clinic at the Centre hospitalier de la Sagamie revealed 26 patients who received surgical orthopedic treatment. Initially, the patients were offered conservative treatment, which consisted of physiotherapy sessions, the wearing of an ankle-foot orthosis or serial casting. When this was unsuccessful, foot surgery was considered. RESULTS: During the study period, 49 orthopedic procedures were done, including 24 triple arthrodeses; of these, 9 were combined with lengthening of the Achilles tendon. Most triple arthrodeses were done in patients between the ages of 30 and 49 years. The surgical options evolved during the study from Lambrinudi arthrodesis through arthrodesis of the ankle to triple arthrodesis with lengthening of the Achilles tendon. CONCLUSIONS: As a complement to conservative treatment, surgery has a place in the care of patients with ARSACS. Clinically, the most effective surgical procedures are triple arthrodesis with percutaneous lengthening of the Achilles tendon and adductor and psoas tenotomies combined with neurectomy of the obturator nerve for perineal hygiene.

Cerebellar allografts survive and transiently alleviate ataxia in a transgenic model of spinocerebellar ataxia type-1.

Spinocerebellar ataxia type 1 (SCA-1) is one of several neurodegenerative diseases, including Huntington's disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and SCA-2, SCA-3, SCA-6, and SCA-7, each caused by an expanded number of CAG repeats in the coding region of their respective genes. The mechanism by which the resulting proteins are pathogenic is unknown. Clinical trials of neural transplants in Huntington's disease patients are under way. While initial reports are encouraging, definitive evidence of graft survival in patients despite the ongoing disease process is not possible with current imaging techniques. Transplants in primates have shown long-term survival of striatal grafts and recovery of function, but have used lesioning to model Huntington's phenotypically. Studies of striatal grafts in a transgenic mouse model of Huntington's have not yet shown a behavioral benefit. We describe a behavioral benefit of cerebellar grafts in a transgenic model of SCA-1 in which the ataxic phenotype results from expression of an expanded ataxin-1 protein. Mice were transplanted at an age when their ataxic phenotype is just becoming evident. Compared with sham-operated littermates, grafted mice showed better performance on multiple behavioral tests of cerebellar function. Differences persisted for 10 to 12 weeks posttransplant, after which there was a progressive decline in motor performance. At 20 weeks postsurgery, donor Purkinje cell survival was evident in 9 of 12 graft recipients. These results indicate that transplants can have behavioral benefits and grafts can survive long-term despite the ongoing pathological process in a brain actively expressing an expanded polyglutamine protein.

A case of cranial meningocele associated with Joubert syndrome.

Joubert syndrome was first reported in 1969 as a rare, recessive autosomal syndrome associated with neuropathological abnormalities of the cerebellum and brain stem, partial or complete aplasia of the cerebellar vermis, and presenting with episodic hyperpnea and apnea, oculomotor abnormalities, and psychomotor retardation. Having experienced one case of this syndrome with associated cranial meningocele, we report the clinical course, MRI features, and surgical findings, and discuss the relevant literature.

Graft-induced restoration of function in hereditary cerebellar ataxia.

Fetal cerebellar cell suspensions, prepared from wild-type (+/+) mice, were implanted bilaterally into the cerebellum of Purkinje cell degeneration' (pcd) mutant mice, a model of adult-onset recessively inherited cerebellar ataxia, to study the functional effects of the grafts on motor coordination and fatigue resistance in a rotating rod treadmill paradigm. The viability of transplanted Purkinje cells was verified with immunocytochemistry for calbindin-D28k and for glutamate receptor 2/3 subunits and with in situ hybridisation histochemistry for insulin-like growth factor I mRNA, biochemical markers normally expressed by Purkinje cells in the cerebellum. Sham injections of vehicle did not appreciably modify the performance of pcd mutants in the rota-rod tests. On the other hand, bilateral cerebellar grafts led to a 3.5-fold increase in the time period that recipient pcd mice were able to stay on the rotating drum based on the comparison of mean scores (of three trials) or a 5.5-fold increase based on the comparison of maximum scores (of the three trials). These findings provide evidence for a motor enhancement in the pcd mouse model of hereditary cerebellar ataxia following intracerebellar transplantation of primordial Purkinje cells.

Fetal tissue grafts for cerebellar atrophy.

It has been shown in a rat model that surgical injury to the right cerebellum with resultant ataxia can be corrected by implantation of embryonic cerebellar tissue into the injured cerebellum. Histological examinations of the cerebellar tissue revealed that mitoses of Purkinje cells of the implanted group were increased substantially over the control group's. The surgically induced ataxia resolved more rapidly in the cerebellar implant group than the control group. Based on this experimental data, a similar technique was applied in 6 patients with severe hereditary cerebellar degenerative ataxia. The preliminary results in these 6 surgically implanted patients with heredity degenerative cerebellar disease show 2 with marked improvement, 3 with moderate improvement and 1 with improvement for 2 months followed by mild deterioration but still better than presurgery. We also studied immunological markers in the blood and CSF in an attempt to determine whether rejection of implanted tissue occurs.