Friday, 30 September 2016

A Sudden,Thunder-like Headache in a Young Patient

A young female presented with a sudden onset of stabbing, occipital headache, which climaxed 
within a few seconds. She described it as the worst headache ever experienced. Maximal pain intensity continued for 2 minutes and then subsided but continued for a further few hours. Headache was associated with mild photophobia and neck stiffness but nevertheless she was able to attend and function at work.

A flu-like prodrome was described over the preceding day, characterized by non productive cough, myalgia and fatigue.


The patient was not on any regular prescribed, over the counter or herbal medications but did admit to occasional cocaine and MDMA use (last intake 3 months ago).  She drank alcohol within safe limits. A cousin had suffered from an intracerebral haemorrhage but no details were known.

The patient presented to her GP surgery and was promptly referred to hospital.

On hospital review she was headache free. Examination was normal. Kernig's sign was negative, although there was some pain on neck flexion.

The differential diagnoses for thunderclap headache remain wide at this stage and include:
1.     subarachnoid haemorrhage
2.     cerebral venous sinus thrombosis
3.     pituitary apoplexy
4.     cervicocephalic arterial dissection
5.     acute hypertensive crisis
6.     spontaneous intracranial hypertension
7.     idiopathic thunderclap headache.

Investigation revealed normal inflammatory markers and unremarkable CT head.
LP  showed WCC <5, RCC < 5, no organisms/growth, CSF protein 0.28g/L, glucose 3.4mmol/L (no serum) bilirubin + pointing to a diagnosis of SAH

After emergency Neurosurgical transfer CT Angiogram was performed. MRI Head and MRA Intracranial did not identify underlying abnormality. Interval outpatient MRI and MRA were planned as an outpatient but after delay in discharge were done 5 days later after complete resolution of the symptoms.  Interval scan confirmed the presence of a para-ophthalmic segment aneurysm.

Some interesting points were discussed at the Neuroscience Meeting:

1. Subarachnoid Haemorrhage and Intracranial Aneurysm

Spontaneous subarachnoid haemorrhage (SAH) in the case presented was caused by a rupture of an intracranial aneurysm, which accounts for the majority (80-90%) of such events.(1) Mortality for untreated aneurysmal subarachnoid haemorrhage is high (50)% within the first month mainly due to risk of re-rupture(2), therefore early identification and definitive treatment of the aneurysm is generally advocated.

Cases of non-aneurysmal spontaneous SAH may be due to:
·       perimesencephalic hemorrhage
·       cerebral artery dissection
·       vascuilitis
·       brain or spinal artery malformations
·       vasculitis
·       stroke
·       venous sinus thrombosis
·       sickle cell disease
·       pituitary apoplexy
·       substance abuse(which could have been perhaps suggested as a culprit in this case considering patient's history of MDMA and cocaine use)
·       reversible cerebral vasoconstriction syndrome

2. CT and MR Angiography as non-invasive technique primary detection tools for detection of aneurysm in SAH

Sensitivity of single slice CTA in detection of intracranial aneurysms has been reported between 77% and 100%, specificity between 79% and 100% (3,4,5) with some (6) claiming that the introduction of spiral CTA achieves “equivalent diagnostic accuracy to that of conventional DSA in the detection of (some) aneurysms”. Some studies, however, have found only 90% sensitivity even with spiral CTA in detection of aneurysms < 3mm.(7) The alternative non-invasive tool for detection of aneurysm in SAH is Magnetic Resonance Angiography. MRA is comparable to CTA for medium and large aneurysms, however in aneurysms smaller than 5 mm, sensitivity decreases to 56% and therefore CTA has been shown to be superior. In addition, discordance between DSA (digital subtraction angiography) and MRA was notable in anterior communicating artery (ACOM) aneurysms.(8)


3. How often does adjunct catheter angiography change management?

In a large study by Tomycz et al, 361 patients underwent DSA (Jan 08-09). Three months prior to DSA, 163 of those had undergone CTA or MRA. These patients had either suffered from acute SAH (65/163) or were seen electively in clinic with diagnosis of ‘presumed intracranial aneurysm’. Based on new information from DSA management plan changed in 17/90 (18.9%) of patients who had undergone CTA and 22/73 (30.1%) who had undergone MRA (which in combination equates to 39/163 (23.9%)). (9)

The most common reason for changing the management plan was a discrepancy in aneurysm size (beyond 5mm) between DSA and non-invasive imaging techniques.

It is interesting, therefore, to see whether this will change clinical practice and indeed, whether it should. Does 24% justify subjecting 76% of other patients, in whom management won't be changed after an adjunct catheter angiography, to such an invasive diagnostic technique, which carries (albeit a small- 2.63%(11) risk of neurologic complications?

4. Yield of LP in CT negative patients (10)

A recent study by Harris et al concluded low yield of LP in patients where CT has failed to diagnose SAH: Out of 2,248 patients identified in retrospective data collection 1,898 CSF samples were suitable for analysis. Out of those 1507 (79.4%) were negative, 299 (15.6%) inconclusive and 92 (4.1%) had CSF positive for bilirubin, of which 8 (0.4%) were diagnosed with aneurysm on further imaging. It's worth noting that 13.2% of samples were un-interpretable due to the presence of oxyhaemoglobin which obscures the bilirubin peak on spectrophotometry.

A new clinical decision tool has been proposed (12):




Of note, age >40 at presentation makes SAH more likely in patients with a typical history. 


References

1. Kirkpatrick PJ. Subarachnoid haemorrhage and intracranial aneurysms: what neurologists need to know. J Neurol Neurosurg Psychiatry 2002;73(suppl 1):i28–i33.

2.Locksley HB. Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations: based on 6368 cases in the cooperative study. J Neurosurg 1966;25(2):219–239.  
3.Chapell ET, Moure FC, Good MC. Comparison of computed tomography angiography with digital subtraction angiography in the diagnosis of cerebral aneurysms: A meta-analysis. Neurosurgery. 2003;52:624–31
4.Cloft HJ, Joseph GJ, Dion DE. Meta-analysis of risks of cerebral angiography in patients with subarachnoid hemorrhage, intracranial aneurysm and arteriovenous malformation: A meta-analysis. Stroke. 1999;30:317–20.
5.HenriĆ«tte E. Westerlaan, J.M.C. van Dijk, Marijke C. Jansen-van der Weide, Jan Cees de Groot, Rob J. M. Groen, Jan Jakob A. Mooij, and Matthijs Oudkerk. Intracranial Aneurysms in Patients with Subarachnoid Hemorrhage: CT Angiography as a Primary Examination Tool for Diagnosis—Systematic Review and Meta-Analysis. Radiology 2011 258:1, 134-145.
6.Hope JK, Wilson JL, Thomson FJ. Three-dimensional CT angiography in the detection and characterization of intracranial berry aneurysms. AJNR Am J Neuroradiol. 1996;17:439–45. 
7.Jacobson DM, Trobe JD. The emerging role of MRA in the management of patients with third cranial nerve palsy. Am J Ophthalmol. 1999;128:94–6.
8.Schwab K, Gailloud P, Wyse G, Tamargo R. Limitations of magnetic resonance imaging and magnetic resonance angiography in the diagnosis of intracranial aneurysms. Neurosurgery. 2008;63:29–35.
9.Tomycz L, Bansal N, Hawley C, Goddard T, Ayad M, Mericle R. “Real world” analysis comparison of non-invasive imaging to conventional catheter angiography in the diagnosis of cerebral aneurysms. Surg Neurol Int 2011;2:134.
10.Timothy J. Kaufmann, MD, John Huston, III, MD, Jay N. Mandrekar, PhD, Cathy D. Schleck, BS, Kent R. Thielen, MD, and David F. Kallmes, MD . Complications of Diagnostic Cerebral Angiography: Evaluation of 19 826 Consecutive Patients. RSNA Radiology 2006; 243(3)
11.Sayer D, Bloom B, Fernando K, Jones S, Benton S, Dev S, Harris T. An observational study of 2,248 patients presenting with headache, suggestice of SAH, who receieved lumbar punctures.
12. Kimura, A, Kobayashi K, Yamaguchi H, Takahashi T, Harada M, Honda H, Mori Y, Tanaka A.Nw clinical decision rule to exclude subarachnoid haemorhage for acute headache; a multicentre observational study. BMJ 2016;6: epud ahead of print

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

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.


Investigations

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.

Saturday, 3 September 2016

London ABN neurology programme for medical students

Medical students should make an effort to attend the ABN. #ABN #NeuroPhobia

If you are medical student and based in London, or close to London, you may want to make arrangements to attend the following session at the next ABN. Please make the effort to go. The only protection against neurophobia is education.