The main challenge in neurology is getting things right and knowing where they are. I know this generic statement might apply to all things medicine, but its importance is amplified in the realm of neurology. I remember one of the lecturers saying that neurology is about two things, respectively being (1) where the lesion is, and (2) what the lesion is. Once these two questions are resolved, everything is plain sailing from there (except rare circumstances where the patient's situation has deteriorated very quickly, like embolic stroke).
The most insuperable difficulties of neurology, thus following, are the ways to resolve the questions. Experienced neurologists will be able to pick up different signs and symptoms through history-taking and physical examination. Some of the ones I met are even able to tell what they're dealing with during history-taking: the way the patient articulates, the content of the said articulation, the gait of the patient as they walk into the room, as well as any abnormal movements like twitches or tics (Tourette's Syndrome, for instance). In this article, I want to deal with the questions one by one. This is always interesting and the answers to the questions can interact directly with each other, since some types of lesions are more likely to be found at particular sites of the brain, thus present conventionally in a finite set of readily-identifiable ways.
This diagram shows two MRI scans (T2 FLAIR, judging by the intensity of the CSF as relevant to the brain parenchyma) taken from a patient presenting with right hemiparesis (right, bilateral limb weakness) and slurring of speech. The scans show a mass hyperintense as compared to the rest of the brain parenchyma, located over the right anterior portion of the brain, covering the frontal and parietal lobes. There are no corresponding lesions on the right side. It is likely that the patient has left ischaemic stroke, possibly involving the middle cerebral artery with sparing of the M1 segment (due to lack of infarct extension to the basal ganglia). One might query the side of the hemiparesis and its relevance to this lesion. Why do they not match? There is a phenomenon called decussation, whereby neural tracts 'cross over' to the other side. It doesn't happen all the time, but in terms of voluntary motor movements, the relevant tracts do, in vast majority, at the level of the medulla oblongata.
This time, we're dealing with Albert Dunnery**, a 70-year old gentleman who presents to the hospital with serious, persistent headaches. He is seen at the out-patient clinic, rather than the A&E department. This information is rather important since we can guess, from the start, the chronicity of symptoms. It also guides our management and the pace of ordering investigations - if the patient presents in the A&E, we better start cracking and think about sustaining the patient's life before we fiddle around with the tests.
Of note, the patient's eyes look weird during the consultation. What's so weird? I'll elaborate on this later.
Patient Profile:
CHIEF COMPLAINT(S) & PRESENTING FEATURES:
Headaches - generalised in location, no radiation to anywhere below the head, persistent and spontaneous onset, first started a few weeks ago (exact time unsure); no previous episodes of comparable headache; dull in quality; 7 / 10 rated on the Visual Analogue Scale (pain scale); slight improvement in terms of severity when resting head on a pillow or armrest (suggestive of amelioration generally when placing head on an inclined position); there are no known circumstances which lead to exacerbation of the current problem;
Vomiting - Onset at around the time the headaches emerge; small amounts of aspiration, with normal food material aspirated (no blood, or any other abnormality); the frequency clocks in at around two to three times daily, where there are no previous episodes before the onset of the headaches. The episodes are of variant frequency, depending on the severity of the headaches;
Dizziness and Disturbed Gait - The patient complains of dizziness for the past few weeks, severe enough to disrupt daily activities whereby the patient usually exits the house with the accompaniment of his family members. It is progressively worse. A walking stick is no longer sufficient. As the patient strolls into the consultation room,
Drowsiness - the patient also complains of worsening drowsiness, where it is hard for him to concentrate in activities of daily living, such as reading and writing. It is much more serious in the past few days than it was before. He has taken more naps than usual and sleeps for, on average, 7 hours at night. There are no significant changes in sleep times.
Constitutional & Anaemic Symptoms: The patient experiences several constitutional symptoms, including night sweats and low-grade fever (remains subjectively felt; upon admission, the patient is not feverish), and anorexic. The patient has not noticed by significant, unexplained weight loss. This might be due to his regular exercising habits. Moreover, there are no anaemic symptoms.
Review of Systems:
(a) Weakness of the left lower limb, independent of the dizziness; the weakness has occurred within the past few weeks and has affected walking;
(b) Dysphagia which is noticed within the past few days, which is described as the inability to initiate the movement rather than any form of obstruction. The patient raises his head when swallowing to aid the descent of foodstuffs and liquid. in compensation of the defect;
(c) Back Pain, which has lasted for the past nine weeks. It does not radiate elsewhere and is persistent in nature. The severity is rated at 6 / 10 on the Visual Analogue Scale. It is dull in quality. It arises spontaneously and is not exacerbated or relieved by any change in posture or any other circumstance. There is no morning stiffness. There is no sciatica.
(d) Cognitive Medley: increased forgetfulness and progressively lowering of attentiveness - the patient cannot concentrate as well (which might be due to the drowsiness).
The patient also has slight slurring of speech, as observed during the consultation.
There are no other identifiable symptoms in the review of systems. More significantly, there is no urinary or faecal incontinence. Nor is there any detected sensory loss (numbness). The upper limbs are also purported to be fine. We cannot entirely take the patient's word for it - once the patient presents with a neurological clinical picture, it is advised to examine the cranial nerves, upper and lower limbs, as well as gait pattern to get a more comprehensive snapshot of the patient's general health status.
PAST MEDICAL HISTORY:
Persistent diabetes mellitus (Type 2), which is purported to be well-controlled, The patient has had the condition for more than twenty years.
No hypertension, autoimmune conditions or any other chronic medical conditions.
PAST SURGICAL HISTORY:
Operation performed on the plantar aspect of the right foot (removal of plantar fibroma) over fifty years ago (unlikely to be significant in this context, but included since the patient presents with gait issues and for the purposes of completeness);
Burr Holes drilled to treat subdural haematoma, which occurred over five years ago. As far as the patient knows, there are no associated complications post-op.
CT Brain showing right subdural haematoma (it is likely that the bleeding is fairly acute, due to that the blood is hyperdense as compared to the brain parenchyma. It causes mass effect, as indicated by the compression of the ipsilateral lateral ventricle to the other side (crossing the midline). This diagram is extracted from BMJ, on URL: https://www.bmj.com/content/bmj/348/bmj.g1682/F1.large.jpg.
FAMILY HISTORY: Both parents died - mother died of subarachnoid haemorrhage, while father died of natural causes. There are no identifiable genetic conditions which run in the family. To the patient's knowledge, no first-degree relative has had cancer before.
DRUG HISTORY: no known drug allergies; no recreational drug use (at least in the past forty five years); the patient takes metformin and dapaglifozin (SGLT2 inhibitor). Both of which are used for controlling diabetes mellitus.
SOCIAL HISTORY:
Non-current-smoker (past smoker, having smoked for forty years; stopped from the past month);
Non-current-drinker (past heavy drinker, having drunk > 20 units every week for the past thirty years; reduced to 6 units [approximately] since last month);
Living with long-term partner, non-sexually active;
No identifiable life stressors that require psychiatric and medical attention.
INFECTIOUS HISTORY: unremarkable.
DIETARY HISTORY: unremarkable.
Physical Examination:
The neurological systems of the upper limbs, lower limbs and cranial nerves are examined. A cerebellar examination is also performed (integrated in the aforementioned examinations). Moreover, as the patient has back pain, I've taken a look at it (Spinal Examination). Ophthalmoscopy is also performed to check for papilloedema.
Vital Signs: High Blood Pressure (even when age-adjusted; note the patient does not have a history of hypertension) - 150 / 110 mmHg, Heart Rate: 48 bpm, Respiratory Rate: 20 breaths per minute. Breathing is shallow. Urinalysis is normal and urinary output is normal. The patient is borderline feverish. The patient also has grossly decreased consciousness, with a GCS decreasing to 7 / 15 (2 + 2 + 3).
The patient also has bruises over both hips and the left lateral epicondyle of the humerus, which are ostensibly related to unsteadiness in gait.
Back Pain: tenderness over L1-L2, localised without radiation; no scars or masses; no overlying skin changes; no issues in spinal alignment; movements of the spine limited by the pain only;
Ophthalmoscopy: Papilloedema present (swollen optic disc indicative of increased intracranial pressure);
Neurological Examinations:
- The patient is drowsy;
- The patient has dilated right pupil which does not respond to light; the left side is normal - later on, both eyes are affected and do not exhibit pupillary light and accommodation reflex responses; the swinging torch test is unremarkable; When testing for eye movements, there is vertical nystagmus bilaterally (up-beating). Eye movements are generally impaired over the right eye, with the eye being inclined to the lateral aspect. This has later deteriorated to a 'fixed' state (inclination to the lateral aspect indicates the early preponderance of the abducens nerve; subsequent deterioration reflects compression effects towards it). The left side shows the same signs more prominently, subsequently. There is also drooping of the eyelids, more prominently on the right side. Soon, even the left side is affected to the same degree.
- The patient has problems with swallowing - CNIX and CNX issue;
- In terms of the upper limbs, there is generally reduced power over the left upper limb (roughly 2/5 on the MRC Scale), where the right side is 3/5 (both deteriorated to 1/5 soon). There is bilateral muscle spasticity. There is impaired coordination. The patient has dolichoectasia and has failed the finger-nose test. There is bilateral hyperreflexia, indicating the presence of an upper motor neurone lesion. The patient is Hoffmann Sign positive (flicking of the finger) (indicative of upper motor neurone lesion). There is no loss in pain sensation bilaterally.
- In terms of the lower limbs, there is generally reduced power over the left lower limb (roughly 1/5 on the MRC Scale), where the right side is 3/5 (both deteriorated to 1/5 soon). There is bilateral muscle spasticity. The patient has failed the heel-shin test bilaterally. There is bilateral hyperreflexia and the patient is Babinski sign positive bilaterally (up-going plantar reflex). There is no loss in pain sensation bilaterally.
- Positive for rebound phenomenon;
- Unable to walk independently - ataxia present; Romberg Test negative; cannot perform tandem walking.
The patient has also been subsequently found to suffer from urinary incontinence. This is postulated to be due to an impact on the bilateral medial micturition centres located over the frontal lobes.
This patchwork of features shown in the physical examinations is very hard to solve. For starters, I am initially confused by why weakness (a motor problem) is only present on one side and the upper motor neurone signs are bilateral. This is outright perplexing.
Ophthalmoscopy showing dilated optic disc, indicative of papilloedema. This is a clinical sign for increased intracranial pressure. The diagram is extracted from Wikipedia.
Diagram illustrating the pathways behind micturition. This diagram is extracted from: https://iiif.elifesciences.org/lax:33219%2Felife-33219-fig1-v1.tif/full/full/0/default.jpg.
Analysis:
At this stage, the patient experiences symptoms mostly related to the pressure within the brain. This includes headaches and vomiting. Regarding the fact that the headaches are persistent and progressive, with generalised involvement and relieved by elevation of the skull, we ought to be thinking about increased pressure within the skull. As explored in previous articles I've written, increased intracranial pressure is due to the addition of 'extra materials' in the brain. The skull is an inflexible box and the brain is a soft organ, made up of neurones and glia. It is impossible to 'stretch' the skull in any way to make room to accommodate extra materials once the sutures are closed (i.e. shortly after birth to toddler period). It is quite worrying that the patient is also experiencing drowsiness since this concerns the faculty of consciousness, utilising a more poetic way of description. Consciousness is controlled by the Ascending Reticular Activating System (or ARAS), comprising four different pathways: pontine-acetylcholine (for sleepiness), and three others for wakefulness- ventral tegmentum-substantia nigra (using dopamine), locus coeruleus-noradrenaline, and nucleus raphe magnus-serotonin. They are located in the brainstem. This means that a mass must have arisen from the brain and this is sufficiently serious to lead to an effect on the brainstem. The more likely theory is that this mass exerts so much pressure that the brain tissue simply goes downwards. This leads to compression of the brainstem.
This is additionally supported by the fact that the patient presents with dysphagia which is characterised by the inability to initiate an action (thus likely to be neurological instead; for conduit-related issues like obstruction, we're more likely to see patients experiencing vomiting and poor nutrition in the long-run). Swallowing is controlled by pharyngeal muscles, which are innervated by the glossopharyngeal and vagal nerves, both of which originate from the inferior portion of the brainstem (aka the medulla oblongata). Any undue compression can lead to dysphagia.
Following this hypothesis further, it also makes sense that the patient experiences some form of dizziness, thereby entailing disturbed gait. Dizziness is due to a problem with the cerebellum, where the cerebellum is responsible for balance and movement regulation. If the mass leads to brain herniation, the correct term for describing the phenomenon where the brain moves from its original position (in this case, downwards), the cerebellum is compressed. It naturally follows that this explains the persistent dizziness.
More importantly, the patient experiences left lower limb weakness, This points towards an issue with the motor cortex, contextualising this in our hypothesis. The frontal lobe might be affected and the mass, following our hypothesis, should be on the right brain (due to decussation). The slurring of speech, as observed during the consultation, gives greater support to our hypothesis, since slurring is inherently a motor problem rather than a sensory problem. It means that there is an issue with the muscles producing speech. It can be a brainstem or cerebellar issue. Or, it can be a motor cortex problem. However, this is less likely since the Broca's Area, the region responsible for the motor branch of speech, is located on the left.
This diagram shows how a mass in the brain (within the cranium, to be more specific), can lead to increased intracranial pressure. This leads to an increase in removal of CSF for compensation. However, once there's nothing to be done for additional compensation, with the upper limit already reached, the intracranial pressure sharply increases. This diagram is extracted from: https://healthjade.com/wp-content/uploads/2019/01/Monro-Kellie-hypothesis-on-intracranial-pressure-2.jpg.
This diagram shows the different ways the brain can be herniated. The mass shown in this diagram is likely to be epidural/subdural (the meninges are not shown) haematoma, whereby the accumulating mass of blood (where coagulation has started) compresses against the brain. Remember that symptoms do not arise from the left brain, even if it's the contact surface with the haematoma. Symptoms arise from the right side instead (so left limb weakness and no response to pain stimuli on the left) since it is 'squashed' by the hard skull surface. This diagram is extracted from Wikipedia.
This diagram shows the ascending reticular activating system, which is responsible for the control of consciousness. The arrows indicate the projections emanating from this system to the cerebrum. The thalamus acts as the brain's 'St Pancras' - essentially a gigantic train station for the relay of nerve impulses. This diagram is extracted from: https://neupsykey.com/wp-content/uploads/2016/06/B9781437704341000931_f068-012-9781437704341.jpg.
The physical exam findings are rather hard to decipher at first. Trying my best, I think the upper motor neurone signs are attributable to cerebellar and brainstem impact by the downward-going brain as the lesion exerts mass effect. The hypothesis that the cerebellum is impacted is stronger if we take into account the patient's gait pattern. Romberg test negative with ataxia, means that the patient has cerebellar ataxia instead of sensory ataxia. There are 6 cerebellar signs to look for, summarised neatly by the acronym: DANISH - Dolichoectasia (impaired coordination of the limbs), Ataxia, Nystagmus (horizontal or vertical or rotatory), Intention Tremor (assessed by the finger-nose test), Slurring of Speech (due to that the cerebellum controls the coordination of muscles), and Heel-Shin Test negative (coordination issue) and Hypotonus (decreased muscle tone). The patient also has a dilated right pupil and drooping eyelid, which point towards a problem with the oculomotor nucleus in the brainstem (on the right). This is followed by subsequent deterioration to include both sides. This leads me to postulate that the mass effect of the lesion is so serious that it affects the right infratentorial structures first, then the left infratentorial structures.
Illustration of the Brainstem Nuclei. The diagram is extracted from: http://what-when-how.com/wp-content/uploads/2012/04/tmp15F28.jpg.
Illustration of the course of the oculomotor nerve. It is more likely for the ipsilateral oculomotor nerve (ipsilateral to the compressing brain lesion) to be affected first, owing to its proximity towards the cerebral parenchyma.
Illustration of the course of the abducens nerve. The abducens nerve can also be easily affected owing to its course through the petrous temporal bone. Any downward herniation of cerebral matter leading to the descent of the pons is likely to lead to compression, therefore incompetence of the abducens nerve. This manifests as impaired function of the lateral rectus muscle (where the eye is thus inclined to the medial aspect). Also extracted from Cranial Nerves 3rd Ed, Copyrighted by 2010 Wilson-Pauwels, Stewart, Akesson, Spacey, PMPH-USA.
The vital signs shall not be ignored. Hypertension, dyspnoea and bradycardia, are the cardinal signs of the Cushing's Triad. This triad occurs especially in circumstances underlying increased intracranial pressure. What really bugs me is the back pain, because it is entirely detached from the neurological symptoms. What does it mean? What is its significance? Moreover, the patient's consciousness is increasingly affected, with a falling GCS Score. This points towards the need of administering treatment straight away.
Having determined the location of the mass (although we do need an initial CT Brain scan to confirm that there is indeed a mass), what about the pathology in question? What is this mass anyway? At this stage, no one can be sure. We can make guesses though. At this point, we're looking into the major pathologies capable of inflicting such a horrible fate. Using the VINDICATE acronym [7], we have the following candidates:
Vascular - I can think of three possibilities, respectively being stroke, aneurysms and arteriovenous malformations (AVMs). Stroke is rather unlikely given the timeframe, whereas arteriovenous malformations remain a possibility. Aneurysmal rupture or large aneurysms do not fit into the clinical picture, since there is no acute onset of very severe headaches (also known as thunderclap headaches).
Inflammatory - Clinical picture not suggestive of an inflammatory aetiology.
Neoplastic - best bet;
Degenerative - not exactly; the patient experiences cognitive symptoms and given the patient's age, this might indicate Alzheimer's Disease. Parkinson's Disease is also possible, given the ataxia. However, these diagnoses are unlikely given the patient's condition.
Idiopathic / Infectious - No history suggestive of infection; the patient is also not experiencing high fever. Idiopathic is just a nicer word for 'we don't know';
Congenital - most unlikely due to the age of the patient;
Autoimmune - autoimmune brain disease is rather rare in general and there is nothing in the patient's history suggestive of an autoimmune aetiology. Multiple sclerosis and neuromyelitis optica do not present in this way, for instance.
Traumatic - the patient has had subdural haematoma before. This is possible, given our hypothesis of brain herniation. Subdural haematoma is also likely to be chronic, as opposed to epidural haematoma, which is acute.
Endocrine - insignificant.
Investigations:
So we've decided to do some investigations to look into the matter. Usually, radiology gives us more valuable information than mere physical examination (not to mention that neurological examinations are notoriously difficult to perform and interpret).
General Tests- Full Blood Count, Coagulation Profile, CRP, ESR, Liver and Renal Function Tests, U&E and random glucose in serum (to see if the patient's diabetic condition is well-controlled), Group & Save and crossmatching;
Lumbar Puncture - testing of opening pressure (indicative of intracranial pressure), protein, glucose (both parameters as relative to blood), cell count and predominant white blood cell type. This is only performed if the CT Brain does not show any space-occupying lesion***.
Nerve conduction studies are not performed - they are better off being used when it's a peripheral issue, such as multiple sclerosis of a limb.
Radiology- CT Brain for initial evaluation. It is instrumental in checking for large infarcts, haematomas and any space-occupying lesions at the first instance. MRI is used later.
Results:
The most significant result is the CT Brain. An MRI evaluation is done immediately after to clarify the findings. We evaluate the radiology findings before moving on to the blood tests which are more sinister.
CT:
- There is a right, anteriorly located, frontal lobe lesion, hyperdense as compared to the brain parenchyma. Moreover, there is surrounding oedema. The mass also shows specks of hypodensity, which are indicative of chronic bleeding;
- The brain herniates downwards due to the mass effect of the lesion, compressing against the brainstem and cerebellum.
MRI:
T1 shows the corresponding lesion (measured at 14.2 cm x 9.5 cm), which is hypointense to the brain parenchyma, without enhancement. Contrast is added to make things clearer, revealing marked bleeding of the lesion and invasion of surrounding blood vessels. T2 FLAIR is used to evaluate the extent of the oedema and the dimensions of the mass. There is brain herniation.
No other masses or abnormalities can be seen.
CT Brain (with contrast added) showing a contrast-enhanced, hyperdense, singular lesion over the right frontal lobe, with surrounding oedema (hypodense to the brain parenchyma). The scan is extracted from: https://s3.amazonaws.com/static.wd7.us/8/89/CT_scan_of_brain_metastasis_12.jpg.
MRI Brain (T1 plus Contrast) which shows a right-sided frontal lobe lesion with surrounding oedema, affecting the frontal lobe and insular ribbon. The left side is (ostensibly) normal. There is slight mass effect since there is observable deviation of the midline to the left. This scan is extracted from: https://assets.cureus.com/uploads/figure/file/3339/lightbox_53e2dac0734211e5a47463c6d6a55d55-FIGURE1edited.png.
MRI Brain (T2 FLAIR) scan showing a heterogenous mass located on the right. It is located over the right parietal lobe. There is surrounding oedema. There is serious mass effect since there is deviation of the midline to the left. The right lateral ventricle is pushed across the midline. Moreover, the mass features subacute bleeding, explaining why it is hypointense to the rest of the lesion. This scan is extracted from: https://neurosciencecriticalcare.files.wordpress.com/2014/04/mri-flair-gbm.png.
CT Brain scan showing brain herniation, where there is distortion of the lateral ventricles. This scan is extracted from: https://image.slidesharecdn.com/brainherniation-141119224558-conversion-gate02/95/brain-herniation-imaging-10-638.jpg?cb=1416437496.
From the aforementioned radiological findings, the lesion is very likely to be a tumour. From this, we've got a problem. Is it a primary or secondary tumour? After all, secondary brain tumours are 10 times more likely to occur than primary brain tumours. Moreover, the most common tumours to metastasise to the brain are lung, breast cancers and melanoma. Renal cell carcinoma is also suggested to commonly metastasise to the brain. These three account for 67 to 80 per cent of all cases. Recent studies have shown that 72.2 per cent of individuals, regardless of histological subtype, have a solitary brain metastasis and approximately 37 per cent have three or more tumours. [9-10]
The blood test results can shed some light on the matter:
Normocytic anaemia (indicative of anaemia of chronic inflammation), leucocytosis;
High Platelets;
High CRP & ESR (inflammatory markers);
Normal liver and renal function tests;
High random glucose in serum (despite the patient claiming not to have eaten for the past five hours).
All these support a diagnosis of cancer, where high platelet levels (thrombocytosis) is lauded recently as a new biomarker for cancer [11].
Subsequent Tests:
Whole Body PET/CT Scan is performed to screen for primaries since the brain tumour might be, at a greater possibility, a metastasis. The presence of back pain and the patient's uncontrolled diabetes mellitus (I tend to trust people and believe they've actually taken the drugs when they allege so) suggest it might be a pancreatic cancer having metastasised to the brain. This is further supported by the fact that the patient has been a heavy drinker and smoker for a very long period of time. Both of which, are major risk factors. Fair enough, pancreatic cancers are usually only detected in the advanced stage and carry very poor prognosis. It is found that 74 per cent of patients with pancreatic cancer die within the first year of diagnosis and, within 5 years, 94 per cent. For cancers with distant metastasis, the five-year survival rate drops to 3 per cent. [12-13, 15] As a side note, the whole body PET/CT Scan is also efficacious in screening for any other metastatic deposits. Seeing that the cerebral lesion is humongous (by subjective standards), and that pancreatic metastases to the brain are not that common, which is found to be at 0.6% [16], it is very likely that other organs are also affected.
Moreover, a Burr Hole is drilled to obtain a biopsy of the brain lesion. Pathological examination is subsequently performed.
At the same time, due to the presentation of the patient, we have decided to initiate symptomatic treatment. The patient is intubated due to high risk of airway collapse. Dexamethasone is given to reduce cerebral oedema and the patient's head is elevated at a 30-degree angle. Hyperventilation therapy is given. This is accompanied by the use of anti-emetics and paracetamol. Mannitol and hypertonic saline are used to decrease the elevated intracranial pressure to more acceptable levels, thereby slowing the progression of brain herniation. Insulin is given to lower the patient's blood glucose. Since the patient also has dysphagia owing to the neurological issue, at the meantime, a 'nil-by-mouth' sticker is stuck at the top of the patient's bed and parenteral nutrition is administered. The patient is also referred to a physiotherapist due to limb weakness.
Results of Subsequent Tests:
PET/CT confirmed the presence of a hypermetabolic (high 18F-FDG uptake) lesion over the tail of the pancreas, which is measured at 4.1 cm x 3.3 cm. Metastatic deposits are also found in the spleen, kidneys and liver. Biopsy confirms that the histological subtype of the brain tumour is adenocarcinoma, in virtue of findings such as the presence of signet-ring cells and high N/C ratios of cells. It is therefore concluded that the brain tumour is a metastasis (or secondary) of the primary, pancreatic cancer. Since there is distant metastasis, it is stage 4 and the only sensible option now is palliative chemotherapy.
CT, MRI (T2) and PET/CT Scans of a brain tumour located over the right frontal lobe, which is adjacent to the anterior horn of the right lateral ventricle. There is also involvement of the corpus callosum. The scan is extracted from: https://www.auntminnie.com/user/images/content_images/sup_mol/2010_07_30_15_55_33_600_PET_CT_MRI_02_450.jpg.
This figure is extracted from: https://pancreas.imedpub.com/18ffdg-petct-imaging-of-the-pancreas-spectrum-of-diseases.php?aid=3846.
FINAL DIAGNOSIS & TREATMENT: METASTATIC PANCREATIC CANCER w/ BRAIN DEPOSITS - Treated with Palliative Chemotherapy.
In terms of palliative chemotherapy, the regimen FOLFIRINOX (fluorouracil, oxaliplatin and irinotecan and leucovorin) is used. It is more superior than gemcitabine monotherapy. Gemcitabine operates through inhibiting an enzyme called thymidylate synthetase, therefore inhibiting DNA synthesis. It has been shown that FOLFIRINOX administration leads to a median overall survival period of 11.1 months, whereas that for patients having received gemcitabine monotherapy is 6.8 months. [14] The response rate for FOLFIRINOX is also much higher, at 31.6 per cent, than gemcitabine monotherapy, at 9.4 per cent.
Albert died peacefully 3 months after the diagnosis, after showing low-grade response to the chemotherapy regimen.
Concluding Remarks:
This case is rather long-winded and has involved many different details. I guess that's the life in neurology. First, we need to know where the lesion is. This is established by clinical history (clinical manifestations and the structures affected) and physical examination. In this case, the picture is massively complicated by manifestations of brain herniation, leading to cerebellar and brainstem dysfunction. Then, we need to know what the lesion is. There are many times when there are multiple possibilities and investigations are required to eliminate them one by one. There are times when it is very direct, exemplified by cases of acute ischaemic stroke. Cancer is usually more convoluted since we need to see if it is primary or secondary. As many cases of brain tumours originate from another source, we need to do whole body PET/CT in order to unearth the primary lesion. The histological subtype of the brain tumour also provides us with clues as to which organ the primary originates. Then, we administer treatment according to the final diagnosis.
Although neurology is one of the most difficult medical specialties, I guess I am irretrievably drawn to it in virtue of its infinite majesty and mystique.
*The cover picture is extracted from: https://jnccn.org/view/journals/jnccn/12/11/1561fig01.jpeg.
**Again, this is a fake patient in a case study I've written to prove a point. No real patient particulars are used in this case study.
***This is a no-brainer. If lumbar puncture is performed despite having unearthed a space-occupying lesion on CT Brain, this risks creating further brain herniation and a more devastating aftermath. Lumbar puncture entails, quite in the literal sense, piercing the dura mater to get into the spinal cord and acquiring a sample of cerebrospinal fluid (CSF). This process causes a suction effect, whereby an attractively large pressure gradient is formed between the brain (where the presence of the mass has led to heightened intracranial pressure) and the cauda equina (with the punctured hole, the pressure is considerably low). The brain therefore descends further. Lumbar puncture is also contraindicated on the grounds of coagulopathy (that's why the coagulation profile is better than not to be ordered) and immunodeficiency (where there is increased risk of infection) or actual spinal skin infection. However, if the patient has HIV, for instance, but desperately requires a lumbar puncture evaluation and there is no reason not to otherwise, prophylactic antibiotics can be given beforehand. Due to issues of access, if the patient has any spinal deformity like severe lateral scoliosis, lumbar puncture is also not recommended. For current consensus guidelines on lumbar puncture in making neurological diagnosis, refer to [17].
References and Further Reading:
[1] Gori S, Inno A, Lunardi, PharmD G et al. 18F-Sodium Fluoride PET–CT for the Assessment of Brain Metastasis from Lung Adenocarcinoma. Journal of Thoracic Oncology. 2015;10(8):e67-e68. doi:10.1097/jto.0000000000000523.
[2] Kaneda H, Okamoto I, Nakagawa K. Rapid Response of Brain Metastasis to Crizotinib in a Patient with ALK Rearrangement–Positive Non–Small-Cell Lung Cancer. Journal of Thoracic Oncology. 2013;8(4):e32-e33. doi:10.1097/jto.0b013e3182843771.
[3] Lemke J, Scheele J, Kapapa T, Wirtz CR, Henne-Bruns D, Kornmann M. Brain metastasis in pancreatic cancer. Int J Mol Sci. 2013;14(2):4163-4173. Published 2013 Feb 19. doi:10.3390/ijms14024163.
[4] Thurtell MJ, Kawasaki A. Update in the Management of Idiopathic Intracranial Hypertension. Neurol Clin. 2021;39(1):147-161. doi:10.1016/j.ncl.2020.09.008.
[5] Schimpf MM. Diagnosing Increased intracranial Pressure. J Trauma Nurs. 2012 Jul-Sep;19(3):160-7.
[6] Procaccio F, Stocchetti N, Citerio G, Berardino M, Beretta L, Della Corte F, D'Avella D, Brambilla GL, Delfini R, Servadei F, Tomei G. Guidelines for the treatment of adults with severe head trauma (part I). Initial assessment; evaluation and pre-hospital treatment; current criteria for hospital admission; systemic and cerebral monitoring. J Neurosurg Sci. 2000 Mar;44(1):1-10.
[7] General Principles. UW Radiology. https://rad.washington.edu/about-us/academic-sections/musculoskeletal-radiology/teaching-materials/online-musculoskeletal-radiology-book/general-principles/. Published 2020. Accessed December 19, 2020.
[8] Lapointe S, Perry A, Butowski N. Primary brain tumours in adults. The Lancet. 2018;392(10145):432-446. doi:10.1016/s0140-6736(18)30990-5.
[9] Ostrom Q, Wright C, Barnholtz-Sloan J. Brain metastases: epidemiology. Handb Clin Neurol. 2018:27-42. doi:10.1016/b978-0-12-811161-1.00002-5.
[10] Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14(1):48-54. doi:10.1007/s11912-011-0203-y.
[11] Mounce L, Hamilton W, Bailey S. Cancer incidence following a high-normal platelet count: cohort study using electronic healthcare records from English primary care. British Journal of General Practice. 2020;70(698):e622-e628. doi:10.3399/bjgp20x710957.
[12] Kaur S, Baine MJ, Jain M, Sasson AR, Batra SK. Early diagnosis of pancreatic cancer: challenges and new developments. Biomark Med. 2012;6(5):597-612. doi:10.2217/bmm.12.69.
[13] Survival Rates for Pancreatic Cancer. Cancer.org. https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html. Published 2020. Accessed December 19, 2020.
[14] Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. New England Journal of Medicine. 2011;364(19):1817-1825. doi:10.1056/nejmoa1011923.
[15] Duell EJ. Epidemiology and potential mechanisms of tobacco smoking and heavy alcohol consumption in pancreatic cancer. Mol Carcinog. 2012;51(1):40-52. doi:10.1002/mc.20786.
[16] Sasaki T, Sato T, Nakai Y, Sasahira N, Isayama H, Koike K. Brain metastasis in pancreatic cancer. Medicine (Baltimore). 2019;98(4):e14227. doi:10.1097/md.0000000000014227.
[17] Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst). 2017;8:111-126. Published 2017 May 18. doi:10.1016/j.dadm.2017.04.007.
[18] Teasdale G, Jennett B. Assessment of coma and impaired consciousness. Lancet 1974; 81-84.
Comments