Intramuscular tetanus neurotoxin reverses muscle atrophy: a randomized controlled trial in dogs with spinal cord injury.

BACKGROUND: Motor symptoms of spinal cord injury (SCI) considerably impair quality of life and are associated with a high risk of secondary diseases. So far, no pharmacological treatment is available for these symptoms. Therefore, we conducted a randomized, double-blinded, placebo-controlled study in dogs with spontaneous SCI due to disc herniation to test whether a reduction of spinal inhibitory activity by intramuscular injections of tetanus neurotoxin (TeNT) alleviates motor symptoms such as muscle atrophy or gait function. METHODS: To this end, 25 dogs were treated with injections of either TeNT or placebo into their paretic hindlimb muscles. Effects of TeNT on muscle thickness were assessed by ultrasound, while effects on gait function were measured using the modified functional scoring system in dogs. RESULTS: Four weeks after the TeNT injections, muscle thickness of the gluteus medius muscle (before median 1.56 cm [inter-quartile range {IQR} 1.34-1.71 cm] and after median 1.56 cm [IQR 1.37-1.85 cm], P-value 0.0133) as well as of the rectus femoris muscle (before median 0.76 cm [IQR 0.60-0.98 cm] and after median 0.93 cm [IQR 0.65-1.05 cm], P-value 0.0033) significantly increased in the TeNT group. However, there was no difference in gait function between the TeNT and placebo groups. The treatment was well tolerated by all dogs without any signs of generalized tetanus symptoms or any spreading of effects beyond the lumbar level of the injected hindlimbs. CONCLUSIONS: With regard to the beneficial effects on muscle thickness, intramuscular injections of TeNT represent the first pharmacological approach that focally reverses muscle atrophy in SCI. Moreover, the study data support the safety of this treatment when TeNT is used at low dose.

Clinical Course and Diagnostic Findings of Biopsy Controlled Presumed Immune-Mediated Polyneuropathy in 70 European Cats.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011-2019). Median age at onset was 10 months (range: 4-120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

Biopsy Characteristics, Subtypes, and Prognostic Features in 107 Cases of Feline Presumed Immune-Mediated Polyneuropathy.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up. In total, nerve and muscle specimens of 107 cats with biopsy diagnosis of presumed autoreactive inflammatory polyneuropathy and 22 control cases were reviewed by two blinded raters for a set of 36 histological parameters. To identify patterns and subtypes of IMPN, hierarchical k-means clustering of 33 histologic variables was performed. Then, the impact of histological parameters on IMPN outcome was evaluated via an univariate analysis to identify variables for the final multivariate model. The data on immediate outcome and follow-up were collected from submitting neurologists using a purpose-designed questionnaire. Hierarchical k-means clustering sorted the tissues into 4 main categories: cluster 1 (44/129) represents a purely inflammatory IMPN picture, whereas cluster 2 (47/129) was accompanied by demyelinating features and cluster 3 (16/129) by Wallerian degeneration. Cluster 4 (22/129) reflects normal tissues from non-neuropathic control cats. Returned questionnaires provided detailed information on outcome in 63 animals. They were categorized into recovered and non-recovered. Thereby, fiber-invasive infiltrates by mononuclear cells and mild fiber loss in intramuscular nerve branches correlated with higher probabilities of recovery. Remyelination in semithin sections, on the other hand, is correlated with a less favorable outcome. Animals grouping in cluster 1 had a tendency to a higher probability of recovery compared to other clusters. In conclusion, diagnosis of feline IMPN from nerve and muscle biopsies allowed for the identification of histologic features that were positively or negatively correlated with outcome.

Subcutaneous seeding following surgical excision of an intracranial meningioma in a cat.

Traditionally patient owners express their concerns that surgical or diagnostic procedures on a tumor may induce metastasis. In pets, this has been documented in only very rare occasions, e. g. needle path metastases after diagnostic fine needle biopsies of urinary bladder or prostatic tumors. Here, we describe a case of subcutaneous seeding of a feline intracranial grade 1 meningioma 6 months after surgical resection. A 10-year-old male neutered domestic shorthaired cat with typical neurological signs was diagnosed with an extra-axial contrast enhancing mass in the dorsal frontotemporal lobes using magnetic resonance imaging (MRI). Transfronto-parietal bone craniotomy was performed and the 24 × 19 × 22 mm large tumor was largely removed. Tumor recurrence after 12 months resulted in a second surgical tumor removal. In addition, 2 subcutaneous masses of 10 × 4 × 4 mm in size were removed at the site of the original surgical site which were fully separated from the recurring meningeal tumor by the intact frontal bone. Histology and immunohistochemistry suggested the same tumor growth in all 4 masses. Most likely the tumor seeding had been caused during the first surgery. After all, the risk of surgical seeding of a benign tumor seems very low.

[Lafora disease in a Beagle - diagnosis and therapy]. / Lafora-Erkrankung bei einem Beagle ­ Diagnose und Therapie.

Lafora disease is an autosomal recessive lysosomal storage disorder leading to an accumulation of toxic glycogen bodies into the cells of the central nervous system and other tissues. In the progressive form of myoclonic epilepsy, clinical signs typically start around 7 years of age. Causal therapy is impossible, however, in the early stages the symptoms may at least be alleviated by modern antiepileptic drugs. In the case reported here, an approximately 7-year-old Beagle presented with daytime-dependent fasciculations, focal and generalized myoclonus ranging up to a brief tonic-clonic seizure. The signs could be triggered and augmented by stress, sounds and light. Histologic examination was performed on biopsy samples of skin, liver, muscle and nervous tissue to test for the clinical diagnosis of Lafora disease. Sarcoplasmic PAS-positive pla®ue deposits typical of Lafora bodies were detected in the muscle biopsies but not in any of the other specimens. Initial treatment with phenobarbital and imepitoin was unsuccessful. However, treatment with levetiracetam significantly alleviated the clinical signs. At time of writing this publication, 2 years following the diagnosis, the now 9-year-old dog shows occasional, stress-related increase in fokal myoclonic seizures. Episodes of collapse or tonic-clonic seizures did not occur to any further extent.

Therapeutic effects of Tetanus neurotoxin in spinal cord injury: a case series on four dogs.

STUDY DESIGN: Case series on four dogs. OBJECTIVES: To determine the alleviation of motor symptoms in spinal cord injury (SCI) by tetanus neurotoxin (TeNT). SETTING: Different Berlin veterinary clinics, Germany. METHODS: We report on the effect of intramuscular injections of low-dose TeNT into paretic hind limb muscles 2-157 weeks after SCI due to lumbar disc herniation in a clinical case series on four dogs. All dogs underwent unsuccessful or incomplete surgical decompression prior to TeNT treatment. TeNT was injected on a compassionate basis. Stance, gait ability and the diameter of the rectus femoris muscle were assessed as parameters. RESULTS: All four dogs improved their stance and three of these dogs improved in gait at 4 and 6 weeks after TeNT injections without evidence of side effects or spreading of TeNT effects. At the same time, the size of the rectus femoris muscle diameter increased considerably as compared with baseline (baseline: 100%; 4 weeks: 148.7% ± 10.9%; 6 weeks: 137.1% ± 7.9%). CONCLUSIONS: Facilitation of α-motor neurons by TeNT injections into paretic hind limb muscles of four dogs improved standing and/or gait abilities and partly reversed muscle atrophy after SCI. The absence of generalized or painful muscle spasms supports the safety of low-dose TeNT. Therefore, TeNT might evolve as a promising therapeutic option for muscle paresis of central origin, e.g. in individuals with SCI, stroke or multiple sclerosis.

Prevalence of syringomyelia in clinically unaffected Cavalier King Charles Spaniels in Germany (2006-2016).

OBJECTIVE: The aim of the study was to investigate the prevalence of syringomyelia in clinically unaffected Cavalier King Charles Spaniels (CKCS) in Germany. MATERIAL AND METHODS: From 2006 to 2016 a total of 339 asymptomatic CKCSs from all over Germany were included. Age ranged from 3 months to 11 years (mean 3.72 years ± 2.17 years). T1- and T2-weighted magnetic resonance images of the head and cervical spine were obtained. RESULTS: Overall, 163 out of 339 (48.1 %) CKCSs showed evidence of syringomyelia. The results (odds ratio of 1.27 per year; p < 0.0001) corroborate the findings of other studies, in which the risk of developing syringomyelia increases with age. CONCLUSION AND CLINICAL RELEVANCE: In conclusion, around half of the dogs within the German CKCS population are affected by syringomyelia. The prevalence of syringomyelia of the German CKCS population is similar to that of the British CKCS population, which is subjected to breeding strategies on the basis of magnetic resonance imaging investigations.