Survival in dogs with meningoencephalomyelitis of unknown etiology with and without lesions detected by magnetic resonance imaging.

BACKGROUND: The prognosis of individual dogs with meningoencephalomyelitis of unknown etiology (MUE) remains difficult to predict. MUE cases with no lesions detected by magnetic resonance imaging (MRI) occur, but it is unknown whether this finding is associated with prognosis. HYPOTHESIS: MUE cases without detectable lesions on MRI have a better outcome than cases with detectable lesions. ANIMALS: Study included 73 client-owned dogs with MUE presenting to Purdue University Veterinary Hospital from 2010 to 2020. METHODS: Retrospective study. Dogs with a clinical diagnosis of MUE were identified by medical record search. MRI reports were reviewed for presence or absence of lesions consistent with MUE. Clinical findings at presentation, treatment, disease-specific survival, and outcomes including rates of remission and relapse were compared between cases with normal MRI or abnormal MRI. RESULTS: Overall, 54 dogs (74%) were classified as abnormal MRI, and 19 dogs (26%) were classified as normal MRI cases. Death caused by MUE occurred in 1/19 (5%) normal MRI dogs and 18/54 (33%) abnormal MRI dogs (P = .016). Median survival was >107 months in both groups, but survival was significantly longer in the normal MRI group (P = .019). On multivariate analysis, abnormal MRI was significantly related to death (hazard ratio, 7.71; 95% confidence interval 1.03-58.00, P = .0470), whereas significant relationships with death were not identified for either the use of secondary immunosuppressive medications or cerebrospinal fluid nucleated cell count. CONCLUSIONS: MUE dogs with no detectable lesions on MRI have reduced disease-related death compared with dogs with abnormal MRI. The presence or absence of MRI lesions in MUE dogs is prognostically relevant.

Krabbe disease successfully treated via monotherapy of intrathecal gene therapy.

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased GALC enzyme activity, normalized psychosine concentration, improved myelination, and attenuated inflammation in both the CNS and PNS. Moreover, AAV-mediated therapy successfully prevented clinical neurological dysfunction, allowing treated dogs to live beyond 2.5 years of age, more than 7 times longer than untreated dogs. Furthermore, we found that a 5-fold lower dose resulted in an attenuated form of disease, indicating that sufficient dosing is critical. Finally, postsymptomatic therapy with high-dose AAV9 also significantly extended lifespan, signifying a treatment option for patients for whom HSCT is not applicable. If translatable to patients, these findings would improve the outcomes of patients treated either pre- or postsymptomatically.