7 ominous signs that suggest you need to see a neurologist

Neurologists spend most of their time diagnosing benign conditions which are curable or treatable, or at least people learn to live with. Every now and then we see people with startling symptoms such as coma, convulsions, neck stiffness, or paralysis. These are obviously concerning to patients and their families who have a foreboding of diseases such as meningitis, epilepsy, and stroke. Serious as these disorders are, they at least announce themselves and show their hands. Many other neurological symptoms unfortunately give no hint of the serious diseases that follow in their trail. That is when things get a bit tricky.

Ominous. Ankakay on Flikr. https://www.flickr.com/photos/ankakay/4101391453
Ominous. Ankakay on Flikr. https://www.flickr.com/photos/ankakay/4101391453

What are these seemingly benign symptoms which jolt neurologists out of their blissful complacency? What are these red flag symptoms that pretend they are grey? Here are my 7 deceptively ominous neurological signs everyone should know about.

7. A numb chin

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 784, Public Domain, https://commons.wikimedia.org/w/index.php?curid=531758
By Henry Vandyke CarterHenry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 784, Public Domain, https://commons.wikimedia.org/w/index.php?curid=531758

This must be the most deceptive sinister symptom in neurology. Not many people will rush to their doctors to complain about a numb chin, but it is a symptom that makes neurologists very nervous. This is because the chin gets its sensory supply from the mandibular branch of the fifth cranial nerve, also called the trigeminal nerve because it has three branches. And neurologists know that, for some bizarre reason, cancers from other parts of the body occasionally send deposits to this nerve. The numb chin syndrome is therefore not to be treated lightly.

6. Muscle twitching

OK, don’t panic yet. We have all experienced this; a flickering of an overused and tired muscle; a twitching of the odd finger; the quivering of the calf muscles in older people. Neurologists call these fasciculations, and they are only a concern if they are persistent, progressive, and widespread. And also usually only if the affected muscles are weak. In such cases neurologists worry that fasciculations are the harbingers of sinister diseases, particularly motor neurone disease (MND), better known in America as amyotrophic lateral sclerosis (ALS) or Lou Gehrig disease. Many people with muscle twitching will however have nothing seriously wrong with them, and many will be shooed out of the consulting room with the label of benign fasciculations syndrome (we love our syndromes, especially when they are benign). There are many other causes of fasciculations, but MND is clearly the most sinister of them all.

5. Transient visual loss

Scott Maxwell on freestockphotos. http://www.freestockphotos.biz/stockphoto/9747
Scott Maxwell on freestockphotos. http://www.freestockphotos.biz/stockphoto/9747

Neurologists often ask people with headache if their vision blurs or disappears for brief periods of time. These visual obscurations are not as dramatic as the visual loss that accompanies minor strokes or transient ischaemic attacks (TIAs). Visual obscurations affect both eyes and last only a few seconds. They are the result of sudden but brief increases in an already elevated pressure in the head. This may occur with relatively benign conditions such as idiopathic intracranial hypertension (IIH), but it may also portend a serious disorder such as a brain tumour.

4. Sudden loss of bowel or bladder control

bubble-1013915_1920

Loss of control down there would surely concern many people, but often not with the urgency it deserves. There are many non-neurological causes of bowel or bladder incontinence, but a sudden onset suggests that it is arising from the nervous system. The worrying diagnoses here are spinal cord compression and spinal cord inflammation (transverse myelitis). These disorders are often associated with other symptoms such as leg stiffness and weakness, but I really wouldn’t wait until these set in before I ask to see a neurologist.

3. Saddle anaesthesia

bicycle-saddle-791704_1920

Whilst we are on the topic of things down there, a related sinister symptom is loss of sensation around the genitals and buttocks, something your doctor will prudently call saddle anaesthesia. This arises when the nerves coming off the lower end of the spinal cord, collectively called the cauda equina, are compressed. The unpalatable condition, cauda equina syndrome (CES), worries neurologists because the compression may be due to a tumour in the spinal canal.

PS: The bicycle saddle is an apt analogy, but if you prefer horse riding, below is an alternative image to soothe your hurt feelings.

 

By BLW - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1956552
By BLW – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1956552

2. A painful droopy eyelid

A droopy eyelid is a deceptively benign symptom which worries neurologists. This symptom, which neurologist prefer to call ptosis, is particularly concerning if it is accompanied by double vision. One worrying disorder which causes ptosis is myasthenia gravis (MG), and this presents with ptosis on both sides. More sinister is ptosis which is present only on one side, particularly if it is painful. This may be caused by brain aneurysms, especially those arising from a weakness of the posterior communicating artery (PCOM) artery. As the aneurysm grows, it presses on the third cranial or oculomotor nerve, one of three nerves that controls the eyeballs and keeps the eyelids open. An aneurysm is literally a time-bomb in the brain as they wield the threat of bursting and causing a catastrophic bleeding around the brain. This makes ptosis an ominous, but also a helpful, neurological symptom.

By Cumulus z niderlandzkiej Wikipedii, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3167579
By Cumulus z niderlandzkiej Wikipedii, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3167579

There are many other causes of ptosis including Horner’s syndrome, so don’t panic yet but get that eyelid checked out if it refuses to straighten out.

 

1. Thunderclap headache

By © Marie-Lan Nguyen / Wikimedia Commons, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=24189896
By © Marie-Lan Nguyen / Wikimedia Commons, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=24189896

thunderclap headache is a symptom that means exactly what it says on the label! Neurologists will ask if the onset felt as if one was hit by a cricket bat. Even though most people have never been so assaulted, almost everyone with thunderclap headache readily agree this is what it feels like. It is such a distressing symptom that it doesn’t strike the afflicted person (pun intended) that their doctors are more concerned about investigating them, then they are in curing their headache. They patient is rushed to the CT scanner, and then subjected to a lumbar puncture. The doctors then heave a huge sigh of relief when the spinal fluid shows no blood or blood products, reassured that the patient has not suffered a subarachnoid haemorrhage (SAH) from a ruptured a brain aneurysm. The patient, who now has just another headache, is left to get to grips with their now, suddenly, very uninteresting symptom. There are many other causes of a thunderclap headache, but a ruptured aneurysm is the most sinister. If you develop a thunderclap headache, don’t wait to see a neurologist…just get to the nearest hospital!

PS: Don’t feel aggrieved if you are across the Pacific; it is also a thunderclap headache if it felt like being hit by a baseball bat!

Baseball bat in sun. Peter Chen on Flikr https://www.flickr.com/photos/34858596@N02/3239696542
Baseball bat in sun. Peter Chen on Flikr https://www.flickr.com/photos/34858596@N02/3239696542

 

Want to check out more ominous signs? Check out Smart handles and red flags in neurological diagnosis by the neurologist Chris Hawkes in Hospital Medicine.

 

Is neurology research finally breaking the resolve of MND?

Motor neurone disease (MND) is, to say the least, dreadful. It also doesn’t help that the terminology neurologists use adds to the distress. West of the Atlantic, amyotrophic lateral sclerosis (ALS) means MND but goes eastwards and it is only a subtype of MND. Thankfully, for most Americans at least, there is no confusion; it is simply Lou Gehrig disease.

By Goudey [Public domain], via Wikimedia Commons
By Goudey [Public domain], via Wikimedia Commons

MND however remains a conundrum for neurologists who are struggling to solve its puzzling riddles. MND researchers continue to toil and sweat, but their efforts are bearing fruits. Take for example the great strides that established the link between MND and the C9ORF72 gene. What are the promising prospects in the world of MND? Here are some.

Associations: Thiamine deficiency and Diabetes 

By Jynto [CC0], via Wikimedia Commons
By Jynto [CC0], via Wikimedia Commons
Should we be on the lookout for thiamine deficiency in patients with MND? This question is prompted by an article in the JNNP which shows an unexpectedly high frequency of laboratory, but not clinical, thiamine deficiency. Titled Thiamine deficiency in amyotrophic lateral sclerosis, the paper reported thiamine deficiency in about 28% of subjects with MND. The authors did not impute any causal association, and there is nothing to suggest that replenishing the thiamine improved outcomes. It is still worth thinking about because people with MND, as the paper emphasised, are at risk of thiamine deficiency.

Another reported association, more difficult to fathom, is the one between MND and diabetes mellitus. The report in the European Journal of Neurology is titled Association between diabetes and amyotrophic lateral sclerosis in Sweden. Why am I sceptical?

Risk factor: Human endogenous retrovirus K (HERV K) 

Retrovirus capsid. A J Cann on Flikr. https://www.flickr.com/photos/ajc1/3269017701/in/photostream/
Retrovirus capsid. A J Cann on Flikr. https://www.flickr.com/photos/ajc1/3269017701/in/photostream/

The cause for MND remains unknown. Risk factors however abound such as smoking and other environmental risk factors. You may now add human endogenous retrovirus K (HERV K) to that list. This is according to a recent paper in Science Translational Medicine titled Human endogenous retrovirus-K contributes to motor neuron disease. The authors report that HERV K is activated in some people with MND, and it is the envelope proteins that cause damage to tissues. The US National Institutes of Health (NIH) think this is an important development, and it released a press statement titled Dormant viral genes may awaken to cause ALS. Scary! Is this important, or just another risk factor? Only time will tell.

Pathology: Neuromuscular junction inflammation 

By Elliejellybelly13 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40798702
By Elliejellybelly13Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40798702

This sounds almost sacrilegious- the thought that inflammation may really play a role in MND. And at the neuromuscular junction (NMJ), not the anterior horn cells. Well, some researchers are ready to commit blasphemy; publishing in Experimental Neurology, the authors showed evidence of inflammation in the muscles and NMJs of rat models of MND. They went further to show that injecting a growth factor called GDNF reduced this inflammation. Do I perceive a potential treatment pathway? Read all about it if you dare, its titled Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS).

Treatment target: TDP-43 protein 

By Emw (Own work) [CC BY-SA 3.0 or GFDL], via Wikimedia Commons
By Emw (Own work) [CC BY-SA 3.0 or GFDL], via Wikimedia Commons
Will MND ever be a curable disease? A big question, but this is the vision of all the hard-working researchers in this field. What are the prospects for a cure? One group of researchers believe the answer is in preventing misfolding of TDP-43, the protein that plays an important role in MND. They set out their case in an article published in Neurotherapeutics titled TDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and Therapeutic Targets. And don’t worry, its free access. The bold abstract says it all: “we present the case that preventing the misfolding of TDP-43 and/or enhancing its clearance represents the most important target for effectively treating ALS”. The proof of the pudding….

Diagnostic test: Nerve ultrasound

By Oleg Alexandrov - self-made with MATLAB, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3036844
By Oleg Alexandrov – self-made with MATLAB, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3036844

Making the diagnosis of MND is not always (make that is hardly ever) straightforward. In the early stages, symptoms are vague, and clinical signs are non-specific. MND also has many mimics. One of such mimics is multifocal motor neuropathy (MMN). To distinguish this and other mimics from MND, neurologist rely on a test called nerve conduction study (NCS). Even this however is not always helpful.

Researchers have now reported that ultrasound may be more sensitive in distinguishing MND from MMN. Another sacrilegious thought! They published their paper in Journal of Neurology with a rather long title: Nerve ultrasound in the differentiation of multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis with predominant lower motor neuron disease (ALS/LMND). Could the diagnosis of MND really be this simple? I am concerned that there were only 16 subjects with MND in the study, all from one centre. Perhaps a randomised, multi-centre, trial will come to the rescue?

Diagnostic biomarker: Brain iron deposition 

By Oleg Alexandrov - self-made with MATLAB, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3036844
By Oleg Alexandrov – self-made with MATLAB, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3036844

Brain magnetic resonance imaging (MRI) is not a test neurologist rely upon to make the diagnosis of MND. Not anymore it seems, going by an article in American Journal of Neuroradiology. The paper is titled A Potential Biomarker in Amyotrophic Lateral Sclerosis. In the article, the authors assessed the amount of iron deposition in the brains of people with MND using the MRI techniques called SWI and DTI. Their findings suggest that the amount of iron in the motor cortex and motor tracts of the brain is a good guide to the presence of MND. If confirmed, this technique will help to reduce the long time it often takes before neurologists confirm their suspicions of MND to patients and their families.

Prognostic biomarker: Neurofilament light chain (NfL) 

Neurofilament and MBP. Dan O'Shea on Flikr. https://www.flickr.com/photos/dan_oshea/4079086197
Neurofilament and MBP. Dan O’Shea on Flikr. https://www.flickr.com/photos/dan_oshea/4079086197

The outcome of MND, poor as it often is, varies quite widely. This is influenced by several factors such as the type of MND, use of the medicine riluzole, and multidisciplinary care. New research suggests that neurofilament light chain (NfL) may be a more sensitive marker of prognosis. This is reported in an article published in Neurology titled Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. The authors demonstrated that patients with MND have much higher levels of NfL than those without the disease. Furthermore, subjects with MND who had the highest levels at the onset had a higher mortality hazard ratio. I think I know what that means.

Prognostic scale: ALS-MITOS predictive system

A paper in the JNNP has proposed a new predictive system for MND called ALS-MITOS, reportedly better than the more familiar ALSFRS-R. The report is titled The MITOS system predicts long-term survival in amyotrophic lateral sclerosis. Most practicing neurologists wouldn’t know the difference because they don’t to use such predictive systems. But MND researchers would be licking their lips at the prospect of a better measure of disease progression; it will make it much easier for them to show that their interventions really do work!

Treatment: Copper 

By Native_Copper_Macro_Digon3.jpg: “Jonathan Zander (Digon3)"derivative work: Materialscientist (talk) - Native_Copper_Macro_Digon3.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7223304
By Native_Copper_Macro_Digon3.jpg: “Jonathan Zander (Digon3)”derivative work: Materialscientist (talk) – Native_Copper_Macro_Digon3.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7223304

There are >100 mutations in the superoxide dismutase 1 (SOD-1), a gene known to cause MND. SOD-1 is an enzyme that binds both copper and zinc, and when defective it results in mutant copper (don’t worry, I’m just finding this out myself). Acting on this hypothesis, researchers came up with a crafty way of delivering normal copper into the central nervous system of  mice modelled with SOD-1 MND. Publishing in Neurobiology of Disease, the authors showed how they achieved this with CuATSM, a chemical that contains copper and currently used for PET scans. CuATSM is readily transported into the nervous system, delivering its copper as it does so.

The paper has a rather cumbersome title: Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SODG93A mice co-expressing the Copper-Chaperone-for-SOD. The result is however anything but. The technique extended the lives of the mice by an average of 18 months. Unbelievable it seems. Any doubts however vanished when, on stopping the treatment, the mice died within 3 months. The finding is exciting enough for Eureka Alert to run the story with the headline New therapy halts progression of Lou Gehrig’s disease in mice. ‘Halt’ sounds very much like ‘cure’, but lets put the brakes on and wait for confirmation in human trials .

Treatment: Gene therapy

Gene_therapy. 1Droid JamLos on Flikr. https://www.flickr.com/photos/jamlos/2734418031
Gene_therapy. 1Droid JamLos on Flikr. https://www.flickr.com/photos/jamlos/2734418031

Every recalcitrant disease is today threatened with gene therapy. Considering it has a long list of genetic risk factors, why should MND be any different? Research taking steps in this direction is therefore long overdue. One such step was published in Gene Therapy and is titled Healthy and diseased corticospinal motor neurons are selectively transduced upon direct AAV2-2 injection into the motor cortex. The authors report that they successfully transduced motor nerves of mice models of MND. In doing so they have set the stage for gene therapy in MND. I don’t claim to understand it all, but it sounds very much like they have set the ball rolling. Promising.

Treatment: Stem cell therapy

By Ryddragyn at English Wikipedia - Transferred from en.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=2148036
By Ryddragyn at English Wikipedia – Transferred from en.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=2148036

Where gene therapy goes, stem cell therapy seems to follow. And this comes from JAMA Neurology with a classic unwieldy academic title: Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis. The content isn’t any easier to interpret, and I will not pretend I get it at all. I comfort myself that it’s all at the ‘open-label, proof of concept‘ stage, and only the very brainy brains need to delve further. But it seems to offer hope.

By Jim Campbell/Aero-News Network - http://www.flickr.com/photos/39735679@N00/475109138/ / http://mediaarchive.ksc.nasa.gov/detail.cfm?mediaid=31873, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3655144
By Jim Campbell/Aero-News Network – http://www.flickr.com/photos/39735679@N00/475109138/ / http://mediaarchive.ksc.nasa.gov/detail.cfm?mediaid=31873, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3655144

 

The sky is surely the limit. Here are a couple of other headlines if you wish to explore further:

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