Eggers, Scott D.Z.

The ocular motor system provides several advantages for studying the brain, including well‐defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBN) and omnipause neurons (OPN) within the brainstem, both types of cells are highly active. Experimental lesions of EBN and OPN cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBN and OPN. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBN and OPN are ensheathed by perineuronal nets (PN), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PN, rather than to the neurons they support, could lead to neuronal dysfunction—such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PN.

Objective (1) To characterize long‐term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium‐sized vestibular schwannoma (VS) using a validated self‐assessment inventory; and (2) to identify clinical variables associated with long‐term dizziness handicap. Study Design Cross‐sectional observational study. Setting Two independent tertiary academic referral centers: one located in the United States and one in Norway. Subjects and Methods All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. Results The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long‐term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long‐term dizziness handicap. Conclusion At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long‐term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship.

Background and purposePrimary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes.MethodsSixteen primary progressive apraxia of speech subjects were age‐ and gender‐matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0‐Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel‐based morphometry and atlas‐based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging.ResultsAll progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy.ConclusionsAlthough neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.

BackgroundThe progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS) are associated with relatively specific patterns of atrophy; the former predominantly involving the brainstem, the latter frontoparietal regions. However, it has become apparent that there are subjects that meet criteria for PSPS and CBS. We refer to subjects with this presentation as Hybrids. The hybrid presentation is not rare, yet there are no studies that have assessed the neuroanatomical correlates of the hybrid syndrome to explain its occurrence.MethodIn this study of 41 subjects and controls, we utilized the technique of voxel‐based morphometry to assess both gray and white matter volume loss in six prospectively recruited Hybrids that underwent 3.0 T volumetric head magnetic resonance image scanning to determine the neuroanatomical correlates of the syndrome. We compared patterns of atrophy in three prospectively recruited groups: the Hybrid group (n = 6), a PSPS group (n = 10), and CBS group (n = 5). All 21 subjects had completed the same standardized batteries assessing cognition, and motor, behavioral, executive, oculomotor and limb praxis function.ResultsThe Hybrid group showed imaging features of both PSPS and CBS, with volume loss observed in the brainstem (superior cerebellar peduncle) and cortex (medial and lateral premotor, prefrontal and motor cortex). As expected, typical patterns of loss were observed in PSPS and CBS.ConclusionsThese findings explain the neuroanatomical basis of the overlapping presenting signs and symptoms of PSPS and CBS, in Hybrids.