Year : 2021 Month : December Volume : 10 Issue : 45 Page : 4054-4057,

A Rare Case of Glioblastoma Multiforme in Association with Alkaptonuria and Ochronosis

Shivakumar K. Masaraddi1, Sreenath G.2

1, 2 Department of General Medicine, S. Nijalingappa Medical College and Hanagal Shri Kumareshwar Hospital, Bagalkot, Karnataka, India.

CORRESPONDING AUTHOR

Dr. Shivakumar K. Masaraddi, Assistant Professor, Department of General Medicine, S. Nijalingappa Medical College & Hanagal Shri Kumareshwar Hospital, Navanagar, Bagalkot-587102, Karnataka, India.
Email : skmneuro@gmail.com

INTRODUCTION

Glioblastoma multiforme is a primary brain neoplasm, consisting of a genetically and phenotypically heterogeneous group of tumours.1 The term glioblastoma multiforme (GBM) was introduced by Cushing in the second half of the nineteenth century, while the first operation on a patient suffering from this type of tumour was conducted in Vienna in 19041. Ninety percent of glioblastoma multiforme cases develop de novo (primary glioblastoma) from normal glial cells by multistep tumorigenesis.1 The remaining 10% of gliomas are cases of secondary neoplasm, developing through progression from low-grade tumours (diffuse or anaplastic astrocytoma’s), which takes about 4–5 years.1 Secondary glioma is diagnosed mostly in persons with the mean age of 39 years, grows more slowly and has a better prognosis.1 Glioblastoma multiforme, which develops de novo, grows within 3 months.1 Although the genetic basis, as well as the molecular pathways underlying development of primary and secondary gliomas are different these two types show no morphological differences.1

Alkaptonuria is an ultra-rare (1:250.000–1.000.000 incidence) autosomal recessive inborn error of catabolism of the aromatic amino acids’ phenylalanine and tyrosine due to a deficient activity of the enzyme homogentisate 1,2-dioxygenase.This leads to the accumulation of homogentisic acid (HGA, 2, 5-dihydroxyphenylacetic acid).2 HGA oxidizes to benzoquinone acetic acid (BQA), which in turn forms melanin-based polymers, deposited in the connective tissue of various organs, causing a pigmentation known as ochronosis, leading to dramatic tissue degeneration.3 A severe form of arthropathy is the most common AKU clinical presentation.4

 

PRESENTATION OF CASE

A 55-year-old male patient came with a history of seizure – had olfactory aura (foul smell sensation) followed by tonic posturing of limbs and loss of consciousness with tongue bite, persistence of foul smell aura even after medication of anticonvulsants with preserved sensorium.

He was a known case of alkaptonuria with ochronosis diagnosed at early forties and no other associated co-morbidities (hypertension, diabetes, smoking) and no other significant past medical, surgical or drug history.

On examination the patient was conscious, oriented. Pulse – 88 b/min, BP – 130/80 mmHg, fundus was normal, pupils were bilaterally equal and reactive to light, cranial nerves were normal, B/L upper limb and lower limb power was 5/5, b/l plantar was flexor.

 

Investigations

MRI Brain Plain and Contrast with Total Spine Screening

Multiple variable sized ring enhancing T1hypointense, T2/FLAIR hyperintense lesions are noted in right fronto-temporal region and insular cortex with marked perilesional FLAIR hyperintense signal and restricted diffusion, largest measuring 10×6×10.4mm in the temporal region, It also shows ill-defined post contrast enhancement. Associated abnormal leptomeningeal enhancement predominantly along right sided sylvian fissure and sulcal spaces of right fronto-temporal region with their effacement.

 

 

All the visualized vertebrae show diffuse T2/STIR heterogenicity with fatty replacement of marrow s/o osteoporosis.

Spondylotic changes in the form of osteophytes seen in whole spine with disc desiccation and marginal osteophytes and reduced disc height at multiple levels: C4-5, C5-6, D2-3, D5, D5-6, D7-8, D11-12, D12-L1 and L4-5 with heterogenous signal in the disc spaces and end plates which reveal calcification on limited CT section -suggestive of ochronosis.