Brain Pathology Case of the Month - June 2018


FINAL DIAGNOSIS

Diffuse glioma exhibiting growth and invasion pattern of gliomatosis cerebri.

DISCUSSION

Tumors may rarely induce parkinsonism either by damaging the thalamocortical pathway (fibers that run from the striatum to the supplementary motor area) or by direct compression of basal ganglia and nigrostriatal structures, such as the midbrain (1, 4). A supratentorial mass, for example, can cause transtentorial herniation and push the margin of the contralateral tentorium against the midbrain, thus inducing parkinsonian features (1, 4). Supratentorial tumors are the most frequent causes of neoplastic parkinsonism, especially meningiomas, although astrocytomas and craniopharyngiomas are also involved (1, 4).

Gliomatosis Cerebri (GC) was deleted from the 2016 WHO classification of central nervous system tumors and it is currently considered just a rare pattern of glioma growth and invasion, characterized by diffuse neoplastic glial cell infiltration involving more than two cerebral lobes, frequently affecting both cerebral hemispheres and occasionally involving the brainstem, cerebellum and spinal cord (3). Moreover, GC usually doesn't exhibit any identifiable mass effect and preserves the architecture of normal surrounding tissues (3). The overall median survival in adult series range from 9.5 to 23.7 months and good prognostic predictors are younger age, low grade tumors, expression of alpha-internexin and IDH1 mutations (3). Clinical features in GC patients are variable, usually presenting as epilepsy, elevated intracranial pressure syndrome, upper motor neuron syndrome, cerebellar ataxia, cranioneuropathies and cognitive deficits (3). Early neuroimaging may not show any prominent abnormalities, especially CT scans, which may delay diagnosis (2, 3). There is no standard treatment for this condition, which is generally based on chemotherapy and radiotherapy, with conflicting results (3).

The occurrence of parkinsonism secondary to GC is rare, with few reported cases (2, 4). Clinical presentations are heterogeneous, with both akinetic-rigid and tremor-dominant presentations possible (2, 4). Rapid progressive parkinsonism with poor response to levodopa was found in all patients, which could be symmetric or not and followed by other neurological signs, such as early cognitive deterioration, Babinski sign, seizures and syncope (2, 4). Clinically, our patient exhibited asymmetric non-levodopa responsive akinetic-rigid syndrome, which is a common feature of neoplastic parkinsonism, but, unlike previously reported cases, he did not present seizures or pyramidal tract dysfunction. Moreover, he presented "red flags" that made a diagnosis of Parkinson's disease improbable, such as frequent falls, incoordination and early cognitive decline, at first prompting suspicion to atypical parkinsonian disorders, especially Lewy body dementia (1, 2, 4).

MRI generally shows involvement of basal ganglia, midbrain, temporal lobe or pons and more than one of these structures can be affected in some patients, given GC infiltrative nature (2). Few to no gadolinium enhancement is common, which contrast with the highly enhancing lesions found in multiple sclerosis and ADEM (3).. When suspected, a brain biopsy should be performed to confirm the diagnosis and define prognosis. Microscopic analysis of our patient showed a diffuse glioma and absence of IDH1 R132H mutation by immunohistochemical analysis, which could suggest non-favorable prognosis (3).

Given its rarity, the diagnosis of gliomatosis cerebri leading to parkinsonism is not readily made. In most of the cases, other diagnosis, like Multiple System Atrophy (MSA) and dementia with Lewy body were considered before. Therefore, one must consider the rapidly progressive evolution of cognitive and motor symptoms, the absence of typical symptoms for MSA and DLB and the poor response to medications in order to consider gliomatosis cerebri.

REFERENCES

  1. Choi KH, Choi SM, Nam TS, Lee MC (2012) Astrocytoma in the third ventricle and hypothalamus presenting with parkinsonism. Journal of Korean Neurosurgical Society.51(3):144-6.
  2. Duron E, Lazareth A, Gaubert JY, Raso C, Hanon O, Rigaud AS (2008) Gliomatosis cerebri presenting as rapidly progressive dementia and parkinsonism in an elderly woman: a case report. J Med Case Reports.2:53.
  3. Greenfield JP, Castaneda Heredia A, George E, Kieran MW, Morales La Madrid A (2016) Gliomatosis cerebri: A consensus summary report from the First International Gliomatosis cerebri Group Meeting, March 26-27, 2015, Paris, France. Pediatric Blood & Cancer.63(12):2072-7.
  4. Ho BL, Lieu AS, Hsu CY (2008) Hemiparkinsonism secondary to an infiltrative astrocytoma. The Neurologist.14(4):258-61.

Contributed by Henrique Soares Dutra Oliveira, Pedro Sudbrack de Oliveira, Victor Calil, Philippe Joaquim Oliveira Menezes Macêdo, Nathalie Canedo, Luiz Felipe Rocha Vasconcellos


International Society of Neuropathology