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Frontotemporal Lobar Degenerations and Related Tauopathies


Corticobasal Degeneration (Rebeiz Disease)

Definition

  • Sporadic neurodegenerative disease characterized clinically by progressive asymmetrical involuntary movements, akinetic-rigid parkinsonism, symptoms of upper motor neuron dysfunction (dysarthria, aphasia), and variable dementia; pathologic findings are atrophy of superior frontal lobes, rostral parietal lobes, basal ganglia, and substantia nigra with widespread neuronal and glial tau inclusions

Clinical Features

Epidemiology

  • Rare, idiopathic disease

  • Affects adults in sixth to eighth decades (mean age 65)

  • No gender or ethnic predominance

  • Estimated incidence <1 per 100,000 individuals per year

Presentation

  • Often nonspecific with unilateral/asymmetrical upper or lower extremity movement abnormalities (stiffness, involuntary jerking, clumsiness, “alien-limb”) or sensory changes

  • 2 to 7 years from initial symptom onset, progression of symptoms to include involvement of previously unaffected limbs, development of apraxia, speech difficulties, hemineglect, and variable cognitive impairment/dementia

Prognosis and Treatment

  • Disease progression to death within 6 to 10 years after symptom onset

  • Patients with a bilateral presentation and dementia have worse prognosis

  • Noncurable, symptomatic treatment only

Imaging Characteristics

  • CT and MRI scans: asymmetrical cortical atrophy of the superior frontal and parietal regions often in region of central sulcus (“peri-Rolandic”) or Sylvian fissure (“peri-Sylvian”)

  • Positron emission tomography (PET) scans may demonstrate asymmetrical decreases in glucose metabolism and blood flow in the superior parietal and frontal lobes, thalamus, and striatum

Pathology

Gross

  • Cortical atrophy tends to involve the superior frontal and rostral parietal regions with relative sparing of the temporal and occipital lobes

  • Pigment loss in the substantia nigra

  • Reduced volume of corpus callosum in more rostral levels

Histology

  • Neuronal loss, gliosis, and superficial spongiosis in atrophic cortical regions

  • “Ballooned” neurons are characteristic:

    • Medium to large pyramidal neurons with ballooned appearance, loss of usual cytoplasmic staining (“achromasia”), variable vacuolation, and proximal dendrite swelling peripheral nuclear displacement, Nissl substance dispersion

    • Found in cortical layers III, V, and VI

    • Can also be found in anterior cingulate gyrus, insular cortex, and amygdala

  • In substantia nigra: neuronal loss with melanophages, remaining neurons may have intracytoplasmic neurofibrillary tangles

  • Threadlike processes may be present in the substantia nigra, locus coeruleus, and at the gray-white junctions

Immunopathology/Special Stains

  • Ballooned neurons are strongly immunoreactive for phosphorylated neurofilament protein

  • Immunoreactivity for phosphorylated tau is most prominent in cell processes of the gray and white matter:

    • Especially striking in fiber bundles of caudate and putamen

  • Tau may be demonstrated focally in cytoplasm of cortical neurons, highlighting threadlike processes and oligodendroglial inclusions (“coiled bodies”)

Main Differential Diagnoses

  • Progressive supranuclear palsy

  • Parkinson disease

  • Multiple system atrophy

  • Pick disease

  • Alzheimer disease

Fig 1, Corticobasal degeneration. Atrophic cerebral cortex of the superior frontal lobe and other affected regions show neuronal loss and superficial spongiosis ( upper left ).

Fig 2, Corticobasal degeneration. Ballooned neurons show reduced cytoplasmic staining with loss of discernable Nissl substance (“achromasia”) and may contain vacuoles.

Fig 3, Corticobasal degeneration. A ballooned neuron demonstrates swelling of proximal a proximal dendrite.

Fig 4, Corticobasal degeneration. Ballooned neurons are strongly immunoreactive for phosphorylated neurofilament protein.

Fig 5, Corticobasal degeneration. Neurons of the substantia nigra may show displacement of normal neuromelanin pigment by abnormal cytoskeletal elements.

Fig 6, Corticobasal degeneration. An immunohistochemical study for tau shows strong cytoplasmic reactivity in a substantia nigra neuron.

Fig 7, Corticobasal degeneration. Cortical neurons may contain irregular clumps or granular tau immunoreactivity.

Fig 8, Corticobasal degeneration. A characteristic feature of the disease is the abundance of tau immunoreactivity of cell processes of the gray and white matter.

Fig 9, Corticobasal degeneration. The caudate nucleus and putamen characteristically contain many tau-positive fiber bundles like the “pencil fibers” shown in the image.

Progressive Supranuclear Palsy (PSP: Steele-Richardson-Olszewski Syndrome)

Definition

  • Sporadic multisystem neurodegenerative disease of middle to late adulthood.

  • Parkinsonism, pseudobulbar palsy, supranuclear ophthalmoplegia, and cognitive decline

  • Neuronal loss, astrocytosis, and tau-pathology primarily involving basal ganglia, subthalamic nucleus, brain stem, cerebellum, and cerebral cortex

Clinical Features

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