An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions

Background The detailed neuropathological features of patients with autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (TCC) and SPG11 mutations are poorly understood, as only a few autopsies have been reported. Herein, we describe the clinicopathological findings of a patient with this disease who received long-term care at our medical facility. Case presentation A Japanese man exhibited a mild developmental delay in early childhood and intellectual disability, followed by the appearance of a spastic gait by age 13. At the age of 25 years, he became bedridden and needed a ventilator. Genetic analysis revealed a homozygous splice site variant in the SPG11 gene (c. 4162–2A > G) after the provision of genetic counselling and acquisition of informed consent from his parents. He died of pneumonia at the age of 44. His brain weighed 967 g and was characterized by a TCC, and his spinal cord was flattened. Microscopically, degeneration was observed in the posterior spinocerebellar tract, the gracile fasciculus, and the posterior column in addition to the corticospinal tract. Marked neuronal loss and gliosis were observed in the anterior horn, Clarke’s column, and hypoglossal and facial nuclei. Various types of neurons, in addition to motor neurons, showed coarse eosinophilic granules that were immunoreactive for p62. The loss of pigmented neurons with gliosis was apparent in both the substantia nigra and locus coeruleus. Lateral geniculate body degeneration was a characteristic feature of this patient. Furthermore, peripheral Lewy body-related α-synucleinopathy and scattered α-synuclein–immunoreactive neurites in the locus coeruleus and reticular formation of the brainstem were observed. Conclusions In patients with hereditary spastic paraplegia with SPG11 mutations, a variety of clinical phenotypes develop due to widespread lesions containing p62-immunoreactive neuronal cytoplasmic inclusions. We herein report the lateral geniculate body as another degenerative site related to SPG11-related pathologies that should be studied in future investigations.

Improving the Quantification of the Lateral Geniculate Nucleus in Magnetic Resonance Imaging Using a Novel 3D-Edge Enhancement Technique

The lateral geniculate nucleus (LGN) is a small, inhomogeneous structure that relays major sensory inputs from the retina to the visual cortex. LGN morphology has been intensively studied due to various retinal diseases, as well as in the context of normal brain development. However, many of the methods used for LGN structural evaluations have not adequately addressed the challenges presented by the suboptimal routine MRI imaging of this structure. Here, we propose a novel method of edge enhancement that allows for high reliability and accuracy with regard to LGN morphometry, using routine 3D-MRI imaging protocols. This new algorithm is based on modeling a small brain structure as a polyhedron with its faces, edges, and vertices fitted with one plane, the intersection of two planes, and the intersection of three planes, respectively. This algorithm dramatically increases the contrast-to-noise ratio between the LGN and its surrounding structures as well as doubling the original spatial resolution. To show the algorithm efficacy, two raters (MA and ML) measured LGN volumes bilaterally in 19 subjects using the edge-enhanced LGN extracted areas from the 3D-T1 weighted images. The averages of the left and right LGN volumes from the two raters were 175 ± 8 and 174 ± 9 mm3, respectively. The intra-class correlations between raters were 0.74 for the left and 0.81 for the right LGN volumes. The high contrast edge-enhanced LGN images presented here, from a 7-min routine 3T-MRI acquisition, is qualitatively comparable to previously reported LGN images that were acquired using a proton density sequence with 30–40 averages and 1.5-h of acquisition time. The proposed edge-enhancement algorithm is not limited only to the LGN, but can significantly improve the contrast-to-noise ratio of any small deep-seated gray matter brain structure that is prone to high-levels of noise and partial volume effects, and can also increase their morphometric accuracy and reliability. An immensely useful feature of the proposed algorithm is that it can be used retrospectively on noisy and low contrast 3D brain images previously acquired as part of any routine clinical MRI visit.

Rodent Area Prostriata Converges Multimodal Hierarchical Inputs and Projects to the Structures Important for Visuomotor Behaviors

Area prostriata is a limbic structure critical to fast processing of moving stimuli in far peripheral visual field. Neural substrates underlying this function remain to be discovered. Using both retrograde and anterograde tracing methods, the present study reveals that the prostriata in rat and mouse receives inputs from multimodal hierarchical cortical areas such as primary, secondary, and association visual and auditory cortices and subcortical regions such as the anterior and midline thalamic nuclei and claustrum. Surprisingly, the prostriata also receives strong afferents directly from the rostral part of the dorsal lateral geniculate nucleus. This shortcut pathway probably serves as one of the shortest circuits for fast processing of the peripheral vision and unconscious blindsight since it bypasses the primary visual cortex. The outputs of the prostriata mainly target the presubiculum (including postsubiculum), pulvinar, ventral lateral geniculate nucleus, lateral dorsal thalamic nucleus, and zona incerta as well as the pontine and pretectal nuclei, most of which are heavily involved in subcortical visuomotor functions. Taken together, these results suggest that the prostriata is poised to quickly receive and analyze peripheral visual and other related information and timely initiates and modulates adaptive visuomotor behaviors, particularly in response to unexpected quickly looming threats.

Spatial Resolution of Suprachoroidal–Transretinal Stimulation Estimated by Recording Single-Unit Activity From the Cat Lateral Geniculate Nucleus

Retinal prostheses are devices used to restore visual sensation in patients suffering from photoreceptor degeneration, such as retinitis pigmentosa. Suprachoroidal–transretinal stimulation (STS) is a prosthesis with retinal electrodes located in the sclera. STS has the advantage that it is safer than epiretinal or subretinal prostheses, as the implant is not directly attached to the retinal tissue. We have previously reported feasibility of STS with animal experiments and clinical trials. However, functional evaluation with neurophysiological experiments is still largely missing. To estimate the spatial resolution of STS, single-unit activities in response to STS were recorded from relay cells in the dorsal lateral geniculate nucleus of cats, and the response probability of the units was analyzed in relation to the distance between the stimulus location and the receptive field of each recorded unit. A platinum electrode was attached to the sclera after lamellar resection, and the return electrode was placed in the vitreous. The stimulating current, which ranged from 50 to 500 μA, was applied between these electrodes, and the probability of spike responses occurring just after retinal stimulation was measured. The distance at half-maximum of response was determined from the collected response probabilities as a function of stimulus intensity for all units characterized by their distances from the receptive field center to the stimulation point. As the stimulation became weaker, this distance decreased to 1.8° at 150 and 100 μA. As another estimation, the radius of 25% response probability was 1.4° at 100 μA. The diameter of the stimulated cat retinal area, 3.6° or 2.8°, corresponds to human visual acuity of 0.005 or 0.007, or finger counting. Considering the lower hazard to the retina of STS and its potentially large visual field coverage, STS is an attractive method for retinal prosthetic device development.