Globular glial tauopathy Type II: Clinicopathological study of two autopsy cases

Abstract

Globular glial tauopathies (GGTs) are four‐repeat tauopathies characterized by the presence of two types of tau‐positive globular glial inclusions (GGIs): globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). GGTs are classified into three different neuropathological subtypes: Types I, II and III. We report two patients with GGTs – a 76‐year‐old woman and a 70‐year‐old man – in whom the disease duration was 5 and 6 years, respectively. Both patients exhibited upper and lower motor neuron signs and involuntary movements, and the latter also had dementia with frontotemporal cerebral atrophy evident on magnetic resonance imaging. Neuropathologically, in both cases, the precentral gyrus was most severely affected, and at the gray‐white matter junction there was almost complete loss of Betz cells and occurrence of GOIs and coiled bodies with numerous neuropil threads. Both patients also showed neuronal loss and GGIs (mostly GOIs) in many other central nervous system regions, including the basal ganglia. Apart from the degree of regional severity, the distribution pattern was essentially the same in both cases. However, GAIs were not conspicuous in any of the affected regions. Based on the morphology and distribution pattern of the GGIs, we diagnosed the present two patients as having GGT Type II. Electron microscopic and biochemical findings in the former were consistent with the diagnosis. Type II cases are reported to be characterized by pyramidal features reflecting predominant motor cortex and corticospinal tract degeneration. The present observations suggest that a variety of neurological features, including dementia, can occur in GGT Type II reflecting widespread degeneration beyond the motor neuron system.

Morphological characterisation of glial and neuronal tau pathology in globular glial tauopathy (Types II and III)

“…However, the ratio of GOIs to GOIs/CBs in Type II was less than that in Type III (Figure S1). Although described previously in Type II , the present study confirmed that in all cases of both Types II and III, the number of tau‐positive oligodendroglial inclusions gradually decreased from higher to lower levels in the pyramidal tracts (internal capsule/cerebral peduncle > pons > medulla > spinal cord) (Figure S2).…”

“…As described below, three of the cases (cases 1–3) had far fewer GAIs in the cerebral cortex than the other three (cases 4–6), a feature that has already been reported , and is considered a representative example of Type III in the 2013 recommendations . Two of the three Type II cases (cases 1 and 2) have been reported recently elsewhere . The clinical features of these autopsied patients are summarised in Table .…”

“…On the basis of the neuropathology, including the morphology of GAIs, predominant occurrence of GOIs and distribution pattern of neurodegeneration , there appeared to be no apparent difficulty in classifying the case as Type II. In other words, we considered that the overall neuropathology did not differ significantly from that of Type II . Therefore, it seemed possible that combination or co‐occurrence of Types I and II pathology in GGT might be revealed in further studies.…”

“…Those of tau‐related pathology are also similarly assessed as 0 = absent; 1 = sparse/mild; 2 = moderate/numerous. a Case 1, 2: cited with modification from Tanaka et al …”

Globular glial tauopathy Type I presenting with behavioral variant frontotemporal dementia

“…[3][4][5] Although the consensus recommendation encourages the detection and subclassification of GGT subtypes for the future establishment of neuropathological and clinical diagnostic criteria, the subclassification of GGT based on actual neuropathological observation is sometimes difficult, and the GGT subtype may not always directly correspond to the clinical symptoms. 6 Tanaka et al (2019) report that in addition to involvement of the motor cortex and corticospinal tract, GGT Type II is impacted by various other central nervous system regions, including the frontotemporal cortices. 7 Another group reported on GGT with a combination of Type I and II pathology.…”