Objective:
To describe a series of 3 cases with communicating hydrocephalus and positive glutamic acid decarboxylase-65 (GAD-65) antibodies, and to explore a potential clinical association between autoimmune neurologic processes and cerebrospinal fluid dysregulation.
Background:
Normal pressure hydrocephalus (NPH) is a clinical syndrome characterized by the triad of gait apraxia, cognitive impairment, and bladder dysfunction in the context of ventriculomegaly and normal intracranial pressure. It can be classified as idiopathic or secondary, depending on if there is an underlying process to explain the hydrocephalus.
GAD-65 antibodies, particularly in higher titers or intrathecal synthesis, are implicated in multiple autoimmune neurologic conditions, including stiff person syndrome spectrum disorders (SPS-SD), cerebellar ataxia, epilepsy, encephalitis, or any combination of these.
There is no literature describing an overlap of these entities
Design/Methods:
Using a research database and clinical referral from treating physicians, we identified three patients who presented with progressive cognitive and gait changes, were found to have imaging findings of communicating hydrocephalus concerning for NPH, and later found to have high-titer GAD-65 antibodies. The electronic medical record was used to review clinical presentations, diagnostics, treatments and outcomes.
Results:
Patients 1 and 2 demonstrated objective gait improvement after a large volume lumbar puncture, and were subsequently treated with ventriculoperitoneal shunt for NPH. Patient 3 did not show improvement after lumbar puncture, and had clinical features more consistent with SPS-SD. All 3 patients were found to have serum GAD65 antibodies > 20 nmol/L. Only patient 2 had CSF tested, which was positive for GAD65 antibodies. Patient 2 and 3 were treated with immunotherapy.
Conclusions:
We highlight a potential association between GAD-65 autoimmunity and communicating hydrocephalus, with implications for the standard workup of a patient with suspected NPH. While causality cannot be established, these findings raise the possibility of autoimmune-mediated disruption of CSF dynamics and warrant further investigation.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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