Wednesday, 21 September 2016

'When the Penny Drops': A Curious Case

A young man in his twenties presented with a six-year history of progressive lower limb symptoms including positive sensory change, poor balance and deteriorating lower limb weakness. 


Examination revealed cachexia and wasting: there was bilateral facial wasting particularly of temporalis as well as wasting of lower limbs proximally and distally. There was bilateral foot drop, flat feet and Romberg’s was positive.

Cranial nerve exam revealed visual acuity of 6/9 on the right with perception to light on left. Corneal scarring was noted with normal retinas. Pupillary response was normal on the right and sluggish on the left. There was also a bilateral 50% ptosis and tarsoraphy.
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Cranial nerves exam revealed visual acuity of  6/9  on the right with perception to light on left. Corneal scarring was noted with normal retinas. Pupillary response was normal on the right and sluggish on the left. There was also a bilateral 50% ptosis and taroraphy.

There was a bilateral decrease in facial sensation and severe bilateral facial weakness. Abnormal audiogram and reduced gag reflex were found. Uvula was, however, central and palate/ tongue normal.
Upper limb examination was normal. Lower limb examination revealed global wasting and areflexia.

Sensory examination revealed absent joint position sense to hips and pin prick exam revealed patchy deficits up to the buttocks.


Routine investigations  as well as vasculitis and infection screen were normal with  CK of 300.  Gangliosides and anti-neuronals as well as genetics for HMN, ALS, FAP, FSHD, MD and SMA were negative.
Muscle biopsy was performed and it showed non-specific fibre atrophy.
Examination of ventricular CSF showed  protein of 4.15 g/L RCC 10,000, WCC 12 (lymphocytes) and normal glucose. Cytology showed RBCs++ and OCB-ve.

NCS and EMG showed no impairment in sensory nerves. There was, however, severe axonal damage noted in motor studies in lower limbs. Facial nerve conduction studies revealed axonal damage, whereas EMG showed neuropathic process with large MUP recruitment (proximal and distal). As on clinical examination, upper limbs were normal.

Imaging revealed infiltrative process with leptomeninges and lumbosacral radiculopathy. It was inconsistent with differential diagnosis of neurosarcoid.
Infection origin was also excluded due to inconsistent timeline of the disease as was amyloid on the basis of negative genetic  testing and blood screen.  Taking this into consideration, the diagnoses of choroid plexus papilloma and lymphoma were suggested.

Choroid Plexus Papillomas and discussion of the case

Choroid plexus neoplasms are rare in all age groups, representing 5 % of all paediatric brain tumours and less than 1 % of adult intracranial tumours.
Most of them are sporadic, yet they constitute component of some syndromes such as Aicardi syndrome, Down syndrome (1)or von Hippel- Lindau disease. Germline mutations of TP53 also seem to predispose to them.(2) As in this case, most of choroid plexus neoplasms arise within the ventricles. (most commonly within the fourth with the lateral ventricles being second in frequency).

Hydrocephalus, the commonest presentation of choroid plexus papillomas, can be produced by a number of different mechanisms: local expansion of the ventricles, spontaneous haemorrhage or by the overproduction of CSF by the tumour itself. Patients present with headache, vomiting and altered mental status or ataxia, as in this case.

Lower limb symptoms are explained by the seeding of CSF and drop metastases which can occur throughout the neuoraxis with particular predominance in cauda equina region. Interestingly, unlike in other neoplasms, seeding also occurs in benign choroid plexus papillomas (as in this patient), however more commonly the spread is achieved by leptomeningeal dissemination. (3)

Choroid plexus papillomas generally have a better prognosis than choroid plexus carcinomas. The latter, more aggresive, have a greater tendency for leptomeningeal dissemination. Favourable outcome can be achieved when gross total resection is combined with adjuvant chemo and radiotherapy.(4) In this case suggested treatment options included removing the primary, resecting metastatic lesion (surgically or stereotactically) as well as adjuvant chemotherapy (Lomustine) and radiotherapy (50 Gy). Limited evidence does show success of chemotherapy with alkylating agents in extensive spinal seeding.

The case emphasized the importance of nerve conduction studies in differentiating between postganglionic (plexopathies, neuropathies) and preganglionic disorders (cauda equina lesions, radiculopathies, posterior column diseases). In case of preganglionic lesion, as in this case, the sensory nerve action potential is normal due to the axonal transport form the cell body to the peripheral axon remaining intact. Furthermore, due to the fact that the cell body of motor nerves is located in the anterior horn of the spinal cord the motor nerve conduction will show abnormality in both types of lesions: preganglionic and postganglionic.

Lastly, the case could be used to support Hickam's dictum, which is in stark contrast to Occram's razor advocating the restriction of differential diagnoses to minimum. Hickman's dictum, on the other hand, encompasses a wider view and allows for the fact that patients can have multiple diseases at the same time. Moreover, it takes into account the fact that they might present with a very rare disease, which would be excluded by firm believers in Occram's razor due to it being statistically insignificant. Which one should we adopt? Is it possible to find a comfortable middle ground?

Learning points:
1) Occam's razor vs Hickam's dictum
2) History key: acquired vs inherited
3) Neurogenic, preganglionic lesions in NCS/ EMG-

Further reading:
1) Hori A, Walter GF, Haas J, Becker H. Down syndrome complicated by brain tumors: case report and review of the literature. Brain Dev. 1992 Nov. 14(6):396-400.
2)Pianetti Filho G, Fonseca LF, da Silva MC. Choroid plexus papilloma and Aicardi syndrome: case report. Arq Neuropsiquiatr. 2002 Dec. 60(4):1008-10. 
3) Menon G, Nair SN, Baldawa SS, Rao RB, Krishnakumar KP, Gopalakrishnan CV. Choroid plexus tumors: an institutional series of 25 patients. Neurol India. 2010 May-Jun. 58(3):429-35. 
4)Wrede B, Hasselblatt M, Peters O, Thall PF, Kutluk T, Moghrabi A, et al. Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study. J Neurooncol. 2009 Dec. 95(3):383-92. 

Enomoto H, Mizuno M, Katsumata T, Doi T : Intracranial metastasis of a choroid plexus papilloma originating in the cerebellopontine angle region : a case report. Surg Neurol 36 : 54-58, 1991.
Kaptanoglu E, Tun K, Celikmez RC, Ozen O, Taskin Y : Spinal drop metastasis of choroid plexus papilloma. J Clin Neurosci 14 : 381-383, 2007.

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