Limbic Encephalitis

Post prepared by Precious Ramirez-Arao, Monmouth Medical Center PGY3

A 60 year-old female was found lethargic lying in a pool of feces by roommate.

EMS was called and was immediately brought to the hospital.

In the emergency department she had a witnessed generalized tonic-clonic seizure.

Her roommate relates she had episodes of confusion and short-term memory loss over the past few weeks.

She remained lethargic over the next 72 hours in the hospital.

48-hour EEG monitoring showed diffuse 2 to 3 Hz delta slowing with periodic lateralized epileptiform discharges emanating from the left frontal temporal region.

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T2 weighted image of the brain showed signal abnormality of the left mesial temporal lobe and the pulvinar with diffusion restriction in the left hippocampus consistent with limbic encephalitis.

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Limbic encephalitis (LE) is a subacute syndrome of seizures, personality change and cognitive dysfunction, typically evolving over days to weeks.

Autoimmune and paraneoplastic forms have been described. The most common neoplasms associated with paraneoplastic LE are lung cancer (usually small cell), thymoma, ovarian or testicular teratoma, breast cancer and Hodgkin lymphoma. The associated autoantibody depends on the tumor type. Lung cancer and thymomas are associated with anti-VGKC while ovarian or testicular teratomas are associated with antiNMDA antibodies.

Neurologic symptoms can precede oncologic diagnosis for several months to years and initial CT scans are typically unrevealing.

Nevertheless, prompt and thorough evaluation for malignancy including PET and CT scan of the chest, abdomen and pelvis should be initiated. Symptomatic treatment includes corticosteroids, plasmapharesis and intravenous immune globulin.

 

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2014, 100th Anniversary for Anosagnosia

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Anosagnosia

Here’s an illustrative example from a conversation with FD, an elderly woman who had had a right hemispheric stroke one week before, leaving her paralyzed on the left side and confined to a wheelchair:

How are you feeling today?

FD: I’ve got a headache.  You know, doctor, I’ve had a stroke so they brought me to the hospital.

Can you walk?

FD: Yes (FD had been in a wheelchair for the past week, and cannot walk)

Mrs D, hold out your hands.  Can you move your hands?

FD: Yes

Can you use your right hand?

FD: Yes

Can you use your left hand?

FD: Yes

Are both hands equally strong?

FD: Yes, of course they are equally strong.

Mrs D, point to me with your left hand.

FD: (Her hand lays paralyzed in front of her).

Mrs D, are you pointing to my nose?

FD: Yes

Can you see it pointing?

FD: Yes, it is about 2 inches from your nose.

Mrs D, can you clap?

FD: Yes, of course I can clap.

Mrs D, will you clap for me?

FD: (She proceeded to make clapping movements with her right hand, as if clapping with an imaginary hand near the midline)

Are you clapping?

FD: Yes, I am clapping.

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The term anosagnosia was first used by Joseph Babinksi on June 11, 1914 in a brief communication presented to the Neurological Society of Paris.

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He described two patients with left hemiplegia who didn’t know they were paralyzed.  The word comes from the Greek words nosos, “disease”, and gnosis, “knowledge”.

Affected patients deny their deficit, and overestimate their abilities, they state that they are capable of moving their paralyzed limb and that they are not different than normal people.

Their false belief of normality persists despite logical arguments and contradictory evidence – they may even produce bizarre explanations to defend their convictions.

If they admit any impairments, they will attribute them to other causes (i.e. arthritis, tiredness, etc.).

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But, this syndrome is not only seen with hemiplegia.

Visual anosognosia or Anton-Babinski syndrome is a rare neurological condition related to cortical blindness.  Affected patients deny their blindness and affirm adamantly that they are capable of seeing. The clinical presentation includes confabulations – instead of admitting blindness, they will make up answers when asked about what they see.

Mr Magoo is a great TV example of Anton’s syndrome – unaware of his loss of vision, he misinterprets and confabulates his way into trouble.

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Anosognosia may occur as part of receptive or Wernicke’s aphasia – affected patients cannot monitor and correct their own speech  errors and may appear angry and frustrated when the person they are speaking to fails to understand them.

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Watch this lecture, by Dr V. S. Ramachandran for more information on this fascinating syndrome:

Neurology of Methamphetamine Abuse, “Feliz Breaking-Bad”!

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Methamphetamine was legally prescribed in injectable form in the US in the 1930-50s as a central nervous stimulant, antidepressant and appetite suppressant (for weight loss).

It became a widely abused prescription drug in the 1960’s, before it became more tightly regulated by the government in the 1970s.

That  is when illegal manufacturing and distribution really started to take off in the US.

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In the 1980s a new crystalline form of methamphetamine, which could be smoked, found it’s way into the US, and quickly started to replace cocaine as the illicit stimulant of choice among drug users.

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Whether snorted, smoked, or injected, methamphetamine rapidly crosses the blood brain barrier where they cause sustained increases in the extracellular concentrations of monoamine neurotransmitters such as  dopamine, norepinephrine, and serotonin.

With repeated use in both humans and experimental animal models, methamphetamine depletes the brain’s stores of monoamines,  contributing to methamphetamine’s high abuse potential – without the drug, users may have an impaired ability to experience pleasure (anhedonia), slipping into a deep depression

Dopamine and serotonin neurons project widely throughout the brain influence a variety of behaviors and functions. Up to 40% of chronic methamphetamine users have memory loss,  impulsive behavior and impaired decision-making.  Continued drug abuse can lead to depression and psychosis.


One interesting aspect of chronic methamphetamine psychosis is the delusion of parasitosis or formication – commonly known as “meth mites”, this is a frequent complaint in heavy daily users of methamphetamine, and can lead to self mutilation:

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AMC’s award winning TV drama Breaking Bad is a well-written and entertaining show that accurately depicts the consequences of moral turpitude and drug abuse:

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However, the show also had it’s lighter movements, here’s our Christmas tribute, Feliz Breaking-Bad or Christmas Meth!:

Kuru (You get it from eating brains!)

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Posted by Dr Abhimanyu Kaura, PGYIII (Medicine), Monmouth Medical Center

Kuru disease is one of the five human spongioform encephalopathies caused by prions.  This group also includes Creutzfeldt-Jakob disease (CJD), variant CJD, Gerstmann-Straussler Scheinker syndrome and fatal familial insomnia.

Bovine spongiform encephalopathy also known as “mad cow disease”, is another prion disease that affects cattle, and was responsible for bringing more attention to all of these disorders in the 1990s.

Kuru is confined the Fore tribes of Papua, New Guinea.

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In the 1950s there were 2100 cases of Kuru in these tribes leading to about 1000 deaths per year.

As per the culture of the Fore tribe, if a person in a family dies his meat is eaten by his family members, especially the wife and children,  as a mark of respect to him.  90% of people affected by the disease were women and children.

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Between 1996 to 2004 only 11 new cases of Kuru were identified in the region. Currently with the ban of cannibalism in the Farah tribes the disease had become virtually non existent.

Kuru first presents with tremors, then unsteady gait and progresses to leg weakness, ataxia, incoherent speech, sporadic laughter finally.  In later stages, affected patients become demented, bed bound and unable to swallow.

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Death occurs most commonly from respiratory distress and pneumonia or infection of pressure sores. The disease is fatal within 1-2  years of the onset of symptoms and had no known cure.

Here’s a video introduction

Watch the full story here:

The causative organism is a prion, a mutated protein which replicates itself like a virus, and is spread by eating the neuronal tissue of infected people.

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The precise incubation period of the disease is unknown, but can be up to fifty years.

The pathological hallmark is the presence spongioform encephalopathy with of Prion reactive plaques mostly in the cerebellum:
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The detailed studies of theses cases of Kuru has helped us understand other prion diseases such as variant CJD, sporadic CJD whose clinical features and course is similar to this condition.

And maybe another link between Zombies and neurology?

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Left world neglected

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Posted by Sanya Naware MSIV, Drexel University College of Medicine

What would it feel like to only perceive one half of the world around you?

For patients with hemispatial neglect, this is an everyday reality.  Hemispatial neglect or hemineglect is a condition in which damage to one hemisphere of the brain causes a lack of awareness of one contralateral side of space.  It is most often a lesion of the right posterior parietal cortex affecting the contralateral side of the body.  The person is unable to recognize stimuli or process them on the affected side.  Left neglect is more common than right neglect because the right hemisphere is able to compensate for the loss of left hemispheric function.

Because these patients only perceive one side, they only draw what we know to be half of an image as seen in the video and image below:

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Lisa Genova, a neuroscientist, expertly describes the daily challenges of living with neglect in her book Left Neglected. It is a difficult condition to imagine and this book does a wonderful job of explaining the realities and frustrations of the patient and her family.

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The main character, Sarah Nickerson, suffers a traumatic brain injury in a car crash.  When she wakes up, everyone around her realizes that she ignores the left side of everything.  Whether it is a clock, a painting, or a room around her, she is not able to recognize the left side of anything.  While she is able to feel the left side of her body, she has to focus on the fact that she has a left side in order to control her left leg and walk.  In fact, when she first sees her left arm, she states that it feels like it belongs to another person, a problem called somatoparaphrenia.  While eating, she only eats the food on the right side of her tray.  She frequently bumps into objects on the left side of her body because she is unaware of their presence.

Sarah’s story is optimistic as her therapist and family use certain tricks to help her adjust.  Some of these methods include placing bright orange tape on the left side of things around their home, using a ruler to guide her to the left side of the page, and wearing shiny jewelry on her left hand to attract attention to it.

Genova ends her book by endorsing the New England Handicapped Sports Association (NEHSA), an organization of volunteers who help people like Sarah find some independence and confidence.

Click here to find out more about right hemispheric brain damage from NEHSA.

References

  1. Genova, Lisa. Left Neglected: A Novel. New York: Gallery, 2011.
  2. Waxman SG. Chapter 21. Higher Cortical Functions. In: Waxman SG, ed.Clinical Neuroanatomy. 26th ed. New York: McGraw-Hill; 2010.

The Neurology of Fright Night

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Everybody knows October is the month of horror movies, haunted houses and Halloween parades.

But, have you ever wondered why we find fear so exciting?

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It turns out that distress and delight are closely related – both are mediated by same deep brain circuit known as the Limbic System.  This system is intimately associated with human emotional behaviors and memory.

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The limbic system is highly interconnected with the brain’s pleasure center, responsible for sexual arousal and the “high” derived from recreational drug use,  The Kluver-Bucy Syndrome, caused by bilateral limbic lesioning, includes heightened sex drive and/or a tendency to seek sexual stimulation from unusual or inappropriate objects.

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Animals with surgical lesions to the limbic system develop abnormal sexual behaviors

Recent studies  have shown these same circuits are responsible for associating fear with memories and the emotional responses that result from triggering those memories.  Patients affected by the extremely rare genetic condition  Urbach-Wiethe disease can develop selective atrophy of the amygdala, becoming fearless, with little or no emotional response to horror films, large spiders or snakes.

This probably explains why horror movies are most popular with younger audiences, mostly teens and twenty-somethings with raging hormones looking for intense experiences:
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So, we go to horror movies to be scared, triggering deep seated pleasure centers within the brain, knowing that we’re actually quite safe from harm, because in an hour or two we’re going to walk out of the theater with no permanent harm done.

Synesthesia: Boy that word tastes good, huh?

Posted by Deepak H. Singh, MS IV Drexel University College of Medicine

Putting my intense desire to describe the mauve affect of a patient, or the loud shirt that a colleague is wearing aside, synesthesia is a fascinating phenomenon in which two or more senses in certain individuals are overlapped, meaning that the experience of both senses is connected in someway.

This has been described in terms of various different senses including forms such as grapheme-color synesthesia in which letters and numbers are perceived as colors, chromesthesia in which sounds are perceived as color, or lexical-gustatory synesthesia in which individual words are perceived as taste sensations in the mouth as alluded to in the title of this blog post.

Click here to find out more about word-taste synesthesia from the BBC.

Some notable supposed synesthetes to perhaps pique your interest are inventor Nikola Tesla, Muscians Eddie Van Halen, Billy Joel, Pharell Williams, and Actor Geoffrey Rush, among others.

This condition has long perplexed neuroscientists who are only touching the surface of the unique neural pathways that may account for the various experiences described by synesthetes.

One school of thought that has gained some traction is the concept of cross-activation, which is made possible by a failure of the physiological process of “synaptic pruning” that occurs in all of our brains during the initial developmental stages.  Synaptic pruning refers to a series of regulatory processes during which various axonal networks that were functional in one stage of development are outcompeted and subsequently eliminated as other synaptic connections become more frequently used as maturation occurs. In synesthetes  it is hypothesized that certain of these connections fail to regress leading to atypical connections between two sensory regions of the brain, thereby opening the door for some pretty vivid sensorial experiences. This, however, has only really held up for sensory regions directly adjacent to one another, as was demonstrated by fMRI studies showing significant brain activity in both the auditory cortex and the fusiform gyrus (responsible for color perception) in synesthetes while no such congruous activity was seen in age-matched controls. Similarly, in one study on lexical-gustatory synesthesia, the lateral sulcus (responsible for taste processing) was activated simultaneously with the auditory cortex in synesthetes.

Another prevailing hypothesis is the concept of “disinhibited feedback“. Normally, signals are travelling in both directions between the primary sensory regions of the brain and those that are involved in organizing that information, and feedback (both positive and negative) is constantly occurring to reconcile all of the different sensory input. If this balance were disrupted, however, it would be possible for signals encountered in the later stage of processing to influence those that were encountered earlier, resulting in the overlapping sensations that are perceived by synesthetes. This, too, may make more sense of the case reports in which individuals with temporal lobe epilepsy or individuals who have just experienced head trauma or stroke to “acquire” a synesthesia-like experience due to some disruption in those pathways, though no concrete studies have been done to test that theory.

Perhaps we’ll never know what is truly occurring at a neuroanatomical level that causes such a curious phenotype. In the meantime, looking at the accomplished list of puported “sufferers” of this condition, it may be worthwhile to pose the following question: which came first the synesthesia or the visionary?