Apraxia Associated With Superficial Siderosis in Cerebral Amyloid Angiopathy

Dear Editor,

Apraxia is a disorder of voluntary movement defined as the inability to make coordinated gestures directed toward a specific position, but with unchanged will and preserved primary sensory and motor abilities. Three different apraxia subtypes have been described: ideomotor, ideational, and limb-kinetic.1 Task-specific apraxia has also been described, which includes speech apraxia, gait apraxia, and apraxia of eyelid opening.2 Apraxia of speech is usually characterized by changes in the quality of speech such as prosody,3 rather than the sound distortions due to ‘articulatory groping’ in the phonetic variant.2 All lesions that affect the gray and white matter of the brain can induce apraxia, and include corticobasal syndrome (CBS), multiple sclerosis, stroke, Creutzfeldt-Jacob disease, Huntington’s disease, and Alzheimer’s disease.4 History-taking and a clinical assessment may allow the clinician to propose the underlying neuropathology, but imaging is still necessary to clarify the diagnosis.

A 72-year-old right-handed female was admitted to the emergency department complaining of acute headache and a tingling sensation in her left hand. Basal computed tomography demonstrated a small subarachnoid hemorrhage (SAH) that involved the right frontal ascending gyrus. Cerebral angiography did not reveal any aneurysms or other vascular malformations. She was discharged 7 days later since the SAH had completely disappeared.

She subsequently developed a complex neurological syndrome characterized by difficulties in motor tasks and language. The lack of ictal onset of these disabilities ruled out a stroke etiology, but the rapid worsening was atypical even for the eventual occurrence of neurodegenerative disease. She continued to experience paroxysmal sensory dysesthesia in her left hand. A formal neurological assessment did not reveal any severe limitation in transitive or intransitive motor tasks. Defects in muscle strength and tone, all sensory modalities, and cerebellar and sensory ataxia were ruled out. These limits were clear when the patient was asked to pantomime either meaningful or meaningless actions (Supplementary Video 1 in the online-only Data Supplement), which did not improve when the examiner himself demonstrated how to perform the task. Simple movements such as showing two or three fingers on request were severely impacted, as was mimicking meaningful common gestures such as the OK sign (Supplementary Video 1 in the online-only Data Supplement). These defects were consistent with ideomotor apraxia. Language difficulties manifested in abnormalities of prosody, speech slowness, sporadic stuttering speech, and phrase segmentation. Semantic speech abilities were intact. She scored 27/30 points on the Mini Mental State Examination and 8/18 points on the Frontal Assessment Battery. Performance on the clock-drawing test, Trail-Making Test parts A and B, and Stroop Color and Word Test were also severely compromised. Verbal, episodic, and autobiographic memories were preserved. Recognition of simplex and complex figures were intact.

18F-labeled fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) revealed a bilateral frontoparietal decrease in radiotracer uptake with no involvement of the occipital lobes, and a striatal dopamine transporter scan produced normal results (data not shown). Brain magnetic resonance imaging (MRI) revealed diffuse leukoencephalopathy involving both the subcortical and deep hemispheric white matter up to the U fibers, with posterior predominance and sparing of the basal ganglia and internal capsule (Fig. 1A and B). Susceptibility-weighted imaging sequences demonstrated diffuse superficial siderosis (SS) in the cortical sulci, subcortical nodular microbleeds, and enlarged cortical vascular spaces (Fig. 1C-F). Both cortical foci and cortical flat deposition were more common in the left hemisphere, especially in the frontal, parietal, and occipital lobes. The absence of aneurysm and arteriovenous malformations, as well as her advanced age supported a diagnosis of cerebral amyloid angiopathy (CAA). Tingling sensations in her left hand were considered “amyloid spells.” Rivastigmine was initiated and slowly titrated up to 9.5 mg/day, which did not affect motor tasks. Levetiracetam at 500 mg BID reduced paroxysmal dysesthesias.

Fig. 1
Brain magnetic resonance imaging. A and B: Coronal T2*-weighted slice (A) and coronal fluid-attenuated inversion-recovery image (B) revealing diffuse subcortical leukoencephalopathy with U-fiber involvement. C-F: Susceptibility-weighted imaging sequences revealing nodular foci of microbleeds (arrows) and superficial siderosis (dashed arrows).

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Apraxia is a leading symptom of CBS and is suggestive of “possible CBS” even when isolated.5 CBS may be sustained by different neuropathological cascades triggered by amyloid β, tauopathies, or TAR DNA-binding protein 43.6 Reasons for such an overlap of apraxia subtypes as common symptoms for different diseases include the involvement of frontoparietal regions encompassing the premotor, motor, and sensory association cortices. Apraxia typically develops contralaterally to the affected brain regions.

SS of the central nervous system manifests in cortical deposition of hemosiderin resulting from blood leakage into the subarachnoid space. The clinical features associated with SS include hearing loss, ataxia, and dementia.7 SS is one of the landmarks of CAA when it is not associated with brain tumors, arteriovenous transformation, head trauma, or anticoagulation. Modified Boston Criteria (version 2.0) for the diagnosis of probable CAA include 1) age ≥50 years, 2) presentation with spontaneous intracerebral hemorrhage, transient focal neurological episodes, or cognitive impairment or dementia, and 3) any combination of at least two of the following strictly lobar hemorrhagic lesions on T2*-weighted MRI: intracerebral hemorrhage, cerebral microbleeds, foci of cortical SS, or convexity SAH with multiple hemorrhages.8 One case of CBS associated with SS due to thalamic cavernoma has been described.9 Both brain MRI and FDG-PET revealed that the SS involved the bilateral frontoparietal cortices in our patient. Hemosiderin deposition within the cortical layers may have led to disconnection of the cortical areas from the basal ganglia and to the inability to effectively and sequentially perform target-specific gestures and motor tasks.10 This paper is the first to report an association between apraxia and SS in CAA.