2013, a 50th anniversary for PSP

Progressive supranuclear palsy (PSP) is often referred to as Steele Richardson Olszewki (SRO) syndrome, after the physicians who first presented the clinical features and neuropathology of the disorder to the American Neurological Association 50 years ago in 1963, followed by a publication in Annals of Neurology in 1964.

PSP is frequently misdiagnosed as Parkinson’s disease, but does have distinguishing clinical features, and distinction is important because treatment and prognosis are very different.

Parkinson’s disease typically presents with unilateral bradykinesia and rest tremor.

In contrast, the initial symptom of PSP is usually a gait problem (“funny walk”) including loss of balance, lunging forward when mobilizing, fast walking with difficulty stopping (festination), and falls. Other common early symptoms include changes in personality, general slowing of movement, slurred speech, difficulty swallowing and visual symptoms. In contrast to Parkinson’s disease, PSP patients have an extended (not flexed) neck, a staring “startled” facial appearance from eyelid retraction and a striking failure of voluntary vertical conjugate gaze.

Actor and comedian Dudley Moore was diagnosed with PSP in 1999, although symptoms had been present for some time before that (perhaps attributed to alcohol), and he died of pneumonia in 2002:

The pathologic hallmarks of PSP is neurofibrillary degeneration (“Tau-opathy”) and atrophy of the midbrain (see MRI images below, A&C normal, B&D PSP).

Midbrain atrophy in PSP (B,D) vs. Normal (A,C)

Midbrain atrophy in PSP (B,D) vs. Normal (A,C)

PSP is a progressive disease and treatment is supportive.  Affected patients do not usually respond to the dopaminergic medications and surgical interventions that are so effective for treating Parkinson’s disease   Physical and occupational therapy can be helpful for balance issues and avoidance of falls. Early identification of problems with swallowing should prompt referral to speech therapy for swallowing assessment and advice on appropriate measures to avoid the complications of aspiration.

Although not formally recognized as a distinct syndrome until 1963, cases of “atypical Parkinsonism” (some of them PSP) were distinguished from more typical Parkinson’s disease by Charcot in the 1880’s.  The figure below shows drawings from one of Charcot’s lectures, given on June 12, 1888 contrasting a typical Parkinson’s disease patient with flexed posture (left) to an atypical Parkinsonian patient who had no tremor and an extended posture (right):

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In sum, early recognition of PSP is important, since the treatment and prognosis are quite different from more typical Parkinson’s disease.

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Christmas Neurology

Christmas Ornament from Cafe-Press

The Christmas Tree Sign
Keyoumars Ashkan and Adrian Casey
J Neurol Neurosurg Psychiatry 1999;67:824
xmas tree
Back pain and sciatica in patients with neurofibromatosis may result from a multitude of pathological processes which include scoliosis, degenerative diseases of the spine, and spinal tumours. Neurofibroma, schwannoma, meningioma, and glioma can all occur. When specific tumours are responsible for the symptoms, surgical excision can offer effective treatment. Many patients, however, have widespread disease. We recently treated a patient with multiple neurofibromas which involved several nerve roots and the cauda equine (figure). The extensive distribution of the tumours produced an MRI picture resembling a Christmas tree. In patients with “the Christmas tree sign” the challenge is in the correct diagnosis of those tumours which produce the symptoms if surgery is to remain a realistic management option.

A Christmas Tree Cataract
E Obi and C Weir
BMJ 2010; 341, (Published 8 December 2010)
A 73 year old woman referred for cataract surgery had on examination a left Christmas tree cataract (fig 1A). Highly reflective, iridescent, polychromatic crystals were noted within the lens. Their colours varied according to the angle of the incident light, (fig 1B, C). We postulate that Christmas tree cataracts result from the accelerated breakdown of membrane associated proteins. The peptides and amino acids accumulate in the lumen of the reticular meshwork, and cystine is concentrated beyond the level of crystallisation, giving rise to growing crystals.

A Christmas Carol: A memorable patient
Stephanie Davies
BMJ. 1998 December 19; 317(7174):1732.
It was a few weeks before Christmas on a dull, chill November morning when Jason and his parents came to see me. As I listened to the, alas, too familiar tale of a young boy, difficult and unreasonable at home who was misbehaving at school, my heart sank and I began to feel as depressed and hopeless as everyone in the room. Jason sat quietly, certainly not demonstrating the hyperactivity suggested by his teacher. Assessment and examination showed that he was a normal and intelligent boy, so was this attention deficit hyperactivity disorder and would the magic pill help?

We discussed strategies to help based mainly on the premise of rewarding good behaviour and ignoring the bad coupled with praise and appreciation. Unfortunately, at this time, there did not seem to be any good behaviour to reward or any achievements to praise.

The review took place some time shortly before Christmas. I sat with prescription pad at the ready, prepared to offer methylphenidate if there was no other way. Jason came in like spring sunshine and his parents were glowing with pride and happiness. What could have wrought this transformation? It seemed unlikely that our previous consultation could have had such a dramatic effect.

I was correct. The magic had been woven by the muse of drama and Charles Dickens. Jason had starred as Scrooge in the school production of A Christmas Carol and was a smash hit. He had even saved the day by playing the part when a less intrepid thespian was incapacitated by stage fright.

Eight months passed before I saw Jason and his father again. With bated breath I inquired about progress. With delight I heard that it had been maintained, culminating in an excellent school report at the end of the academic year.

How important it is for us all to have some measure of success and how I wish all my patients could be a star for a day. I was certainly grateful that Jason and his parents allowed me to share his success. It has been one of my most memorable Christmas presents.

The Christmas “Clacker”
David Strachan
BMJ. 1994 December 24; 309(6970): 1747.
A 44 year old occasional drinker presented to the accident and emergency department at 5 30 am on New Year’s Day. A sensation at the back of his throat was causing a slight discomfort on breathing. On examination his uvula was found to be swollen. He had suffered the same problem on Christmas Day morning the previous year, the common factor being alcohol consumption during the previous evening. It is well known that alcohol consumption triggers or worsens snoring. Overindulgence causes muscle hypotonia and depression of the arousal mechanisms, leading to many people sleeping flat on their backs rather than on their sides. This narrows the airway and leads to a tendency to obstruction. If a kick in the back from a disgruntled partner does not rectify the situation and the “comatose” state persists then forced inspiration through a narrowed airway causes repeated trauma of the uvula and swelling.

Convulsions at Christmas
S Kirker
BMJ. 1992 December 19; 305(6868): 1580.
A healthy 26 year old butcher described convulsions without warning or focal onset between 11 am and noon on Christmas Eve in 1987, 1988, 1989, 1990, and 1991. He had no other convulsions or episodic symptoms that could be epileptic in origin and he had no relevant medical history. His usual working day was from 7 am to 6 pm but for the 14 days before Christmas he worked until at least 10 pm and as late as 1 am, seven days a week. He worked all through the night of 23 December. He did not miss any meals, and ate through the night as well. His usual alcohol consumption was 35 units a week but he drank less during these weeks. Results of examination and computed tomography were normal. Electroencephalograms in 1989 and 1992, each three months after the period of sleep deprivation, showed paroxysmal generalized spike and wave activity at 8 Hz, with a normal background rhythm. The patient was not prepared to change his working hours during the busiest time of year so we prescribed phenytoin over the second half of December. His electroencephalogram suggested he had an underlying tendency to have seizures, which only became apparent when his “seizure threshold” was lowered by sleep deprivation.

Neuro-Behcet’s Disease

This 38 year old woman came to the ED with a 2 wk history of progressively escalating headache. After she was admitted, she complained of L sided numbness, clumsiness and weakness.

Three yrs before this, she had developed a painful monarthritis of the left knee with acute erythema nodosa. Six months later she developed oral and vaginal ulcers, and she was diagnosed with Bechet’s disease and treated for 1-yr with colchicince. She had no recent symptoms from Bechets. She also had a histry of classical migraine headaches.

Her exam showed L facial weakness, L pronator drift, and L sided dsymetria.

Her brain CT was normal. Her lumbar puncture showed a marked pleocytosis with almost 500 WBC, half polys. MRI of the brain showed a mildly ring enhancing lesion that extended from the R midbrain into the R thalaus:

She was treated with high dose intravenous steroids and her symptoms improved over the next 5-days.

Bechet’s disease is a rare immune-mediated systemic vasculitis that presents with oral aphthous ulcers, painful genital ulceration around the anus, vulva, or scrotum and erythema nodosum, and uveitis.
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Neurological involvement can include aseptic meningitis to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome manifesting with confusion, seizures, and memory loss. Brainstem lesions, particulary lesons extending from the midbrain into the diencephalon, as in our case, are most common.
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Neuro-Behcet’s patients are usually treated with corticosteroids. Azathioprine, cyclophosphamide, chlorambucil and cyclosporin A are often added as steroid sparers, because relapses are common when steroids are discontinued.

Diagnostic testing for Alzheimer’s?

The only definitive test for Alzheimer’s disease is examination of brain tissue (usually obtained at autopsy) for identification of the characteristic pathologic changes of Amyloid paque and Neurofibrillary tangles:

Alzheimer’s disease is usually diagnosed based on  clinical criteria, but many patients diagnosed this way are later found to have other causes of dementia when their brains are examined at autopsy, in other words they were misdiagnosed as Alzheimer’s.


With more effective new therapies on the horizon, it is going to become more important to establish a diagnosis of Alzheimer’s more accurately and earlier, perhaps even pre-symptomatically (i.e. mild cognitive impairment or MCI), so that treatment to reverse the build up of plaque and tangles is more likely to be effective.

There has been interest in Apoprotein E (APOE) genotype and Alzheimer’s risk. APOE genes come in 3 types (2-4).  If you have 2 copies of  APOE4 (1-2% of the population)  you are 15 times more likely to develop Alzheimer’s than averages, and if you have one copy of APOE4 you have are 3 times more likely to develop Alzheimer’s than average.   Clearly, there is an association between APOE4 genoytpe and Alzheimer’s.  However, not every patient with APOE4 develops Alzheimer’s, and you can develop Alzheimer’s without APOE4, so APOE genotyping is not recommended as a diagnostic test.

The ratio of cerebrospinal fluid levels of beta-amyloid and tau proteins can be predictive for Alzheimer’s, but this test requires a lumbar puncture, and is inconclusive in many cases.

Magnetic resonance imaging (MRI) of the brain has shown selective atrophy of the hippocampus in patients with early Alzheimer’s (a) vs. normal elderly controls (b), and this technique has been proposed as a diagnostic test for Alzheimer’s, but requires special computerized imaging processing not available at most imaging centers.

Fluorodeoxyglucose posititon emission tomogrpahy (FDG-PET) shows reduced metabolic activity (uptake of sugar) in the temporal and parietal lobes of patients with early Alzheimer’s (these regions are darker) vs. normal elderly controls (these regions are brighter), and this test is FDA approved, covered by Medicare, and widely available at imaging centers around the counrty:

A recent study compared the results of MRI, FDG-PET and analysis of CSF biomarkers  in 97 MCI patients, to see which was best for predicting who would convert to Alzheimer’s first. During a mean follow-up of almost 3-years, 43 patients progressed to AD and 54 did not. Of the 3 tests, an abnormal FDG-PET was most predictive.

Before you all rush out and get your FDG-PET to see if you are high risk for Alzheimer’s, be warned that results may be unreliable when the test is performed at an inexperienced center. Data presented at this year’s American Academy of Neurology meeting showed that up to 2/3 of patients referred to a University dementia program had been misdiagnosed with Alzheimer’s dementia based on misread FDG-PET scans performed at community imaging centers.

The Amyvid™ (Florbetapir F 18) PET scan, which was FDA approved this year, actually quantifies the amount of amyloid plaque in affected patients’ brains (bright), and is probably a more promising new PET technique for predicting Alzheimer’s disease. However, this test is not yet covered by Medicare or other insurance covering, and costs between $1500 and $3000:


In sum, the hope for the future is that with earlier and more accurate diagnosis, future treatments could target Alzheimer’s in its earliest stages, before irreversible brain damage or mental decline has occurred.  However, it is clear that none of the available diagnostic tests are perfect, and although promising, amyloid plaque PET scans are not yet covered by Medicare, so for now we mostly continue to make do with clinical diagnostic criteria.

So you have carotid stenosis, should you have surgery?

Carotid endarterectomy is surgery to remove atheroma (plaque build up) that causes narrowing (stenosis) in the artery to lower the risk for future TIA (transient ischemic attack) and stroke.

So, it seems simple, you’ve been found to have carotid artery disease, you have surgery to “fix it” and reduce your future stroke risk, right?

Well, you guessed it, it’s not that easy.

First, some facts about carotid artery disease and stroke:

Each carotid endarterectomy surgery costs about $15,000.

When you undergo surgery, there is a surgical risk (of stroke or death) which you pay up front, in exchange for a cumulative annual stroke rate reduction (%/yr) for the remainder of your life.

A good analogy is taking out a mortgage.  Doing surgery can be compared to paying points on your new mortgage to lower the future interest rate.  Your more likely to do it for a 20y that for a 5y mortgage.

Whether the benefits of surgery exceed the risk, whether it is worth paying points on your mortgage, and will depend on:
1. The actual risk of surgical complications at your center
2. Your age (i.e. future life expectancy),
3. The degree of carotid stenosis,
4. Most importantly, if you have had a TIA or stroke in the vascular territory of the affected artery within the previous 6-months – referred to as a symptomatic carotid stenosis.

This is how the degree of carotid stenosis is calculated, 1-a/c * 100:

Surgery will reduce the risk of stroke from 26 to 9% over 2yrs
That’s a “relative risk reduction of 60%”
You have to treat 6 pts to prevent 1 stroke/2yr
Or, treat 2.4 pts to prevent 1 stroke/5yrs

Surgery will reduce the risk of stroke from 22 to 16% over 5 yrs
That’s a “relative risk reduction of 30%”
You have to treat 16 pts to prevent 1 stroke/5yrs

Surgery will reduce the Risk of stroke from 10 to 5% over 5yr
That’s a “relative risk reduction of 50%”
But, you have to treat 20 pts to prevent 1 stroke/5yrs

There is no benefit from surgery

The above data is abstracted from the NASCET and ACAS studies, and are based on a surgical complication rate of <6% for symptomatic and <3% for asymptmatic cases. Complication rates can be as high as 10% at some centers. Click here to find your hospital, and look up the complication rate from carotid surgery.

All patients with symptomatic carotid stenoses >70% are probably going to benefit from surgery, even more so if they get to surgery within 2 weeks of their TIA or stroke.

Most patients with symptomatic carotid stenoses in the 50-70% range will benefit from surgery, if it is done at a center where the surgical complication rate is <6%, and they have a life expectancy of >5 years.

The benefits of surgery for an asymptomatic carotid stenosis identified on a routine screening study are much less certain. You can bet the surgeon will tell you that he/she can reduce your future stroke risk by 50%, but all they are really doing is increasing your chance of not having a stroke from 90 to 95% over the next 5 years, so if you are in your 80s or at a center where the complication rate from surgery is >5%, you’re probably not going to break even, and would do better to stick with medical therapy.

Remember to ask these questions before signing up for surgery.

Oral Drugs for MS


There are now 2 FDA approved oral drugs available for the treatment of relapsing remitting MS, teriflunomide (Aubagio, Genzyme/Sanofi) and fingolimod (Gilenya, Novartis).

In the past disease modifying treatments for relapsing-remitting MS all needed to be delivered by injection, and many patients went untreated because of fear of needles, or because of injection site reactions or other side effects with each dose of the mediction, sometimes felt to be worse than symptoms from the underlying disease.

Fingolimod was approved by the FDA in Sept 2010, based studies showing less brain lesions on serial imaging studies, and reduced rates of clinical relapses and progression of disability in patients treated with the drug compared to those on placebo and interferon beta. Patients starting fingolomid do need heart rate monitoring after their first dose, eye exams at basele and after 3 months to detect macular edema (a rare side effect of the drug), and zoster vaccination for those who are not already immune.

Teriflunomide showed less brain lesions on serial imaging studies and reduced clinical relapse rates compared to placebo in clinical trials. The most common side effects were diarrhea, abnormal liver tests, nausea, and hair loss. Treated patients need liver function tests at basleine and periodically during treatment.

Unoftunately, we don’t have head-to-head trials directly comparing the efficacy of these two drugs.

So which drug would I choose? Well, I might be more inclined to recommend teriflunomide for patients with a history of cardiac arythmia or for those taking blood pressure medications such as propranolol or verapamil which can also lower the heart rate. I might be more inclined to use fingolimod in patients who taking other drugs that can affect the liver.

Neither drug is approved for use during pregnancy, although teriflunomide has a stronger warning (category X) of teratogenicity from the FDA.

In sum, we now have two oral medications available for MS patients who have previously been unable or too afraid to get treated with an injectable medication, and this can only continue to improve the long term prognosis for this disease.

Radiation from unnessary CT scans

CT or CAT (Computed axial tomography) scans use computer processed rotating x-ray images to create a detailed cross-sectional image (tomograph) of an organ or body part.

The use of CT has increased exponentially over the last 20 years, and more than 72 million scans were performed in the United States in 2007 compared to only 3 million in 1980.

The use of CT scanning only continues to grow. Doctors are increasing using chest CT to screen for lung cancer, CT based “virtual” colonoscopies to check for colon cancer, CT angiography of the coronary arteries in place of simple exercise stress tests, and CT angiography of the carotid arteries in place of safer duplex ultrasound and MR (magnetic resonance) angiography.

The radiation exposure from a sigle CT scan is equivalent to about 750 chest x-rays.

It is estimated that 0.4% of current cancers in the United States may be from exposure to radiation from CTs performed in the past, and that this may increase to 2% (or 29000 future cancers) as a consequence of 2007 rates of CT usage.

Click here to link Dr Eric Topol’s recent Medscape commentary on the runaway use of CTs.

Click here for a recent Washington Post article on the risk of repeated CT scans in children.

Click here for a statement from the American Academy of Neurology on unnecessary diagnostic testing.

CT can still have some advantages over MR imaging of the brain – it is more readily available and faster in the emergency setting, and can be done in patients who have a contraindication to MR imaging like a pacemaker or other metal implant.

However, it is one of our goals at Monmouth Neuroscience Institute to reduce unnecessary diagnostic testing wherever possible. We strive to avoid doing both CT and MR scans on neurological patients by seeing TIA patients  in our outpatient TIA Rapid Evaluation Center(TREC).  TREC patients can avoid an emergency room visit and CT scan in favor of an elective MR scan, which not only gives  more information, but also avoids an unnecessary dose of radiation.

Benign Paroxysmal Positional Vertigo

Benign Paroxysmal Positional Vertigo (BPPV) is a common cause of dizziness, accounting for 1 in 5 of all cases of dizziness, and more than half of all cases of dizziness in the elderly.

Correct diagnosis is important, because this disorder can usually be easily corrected in a doctor’s office.

BPPV is caused by debris which has collected in in the inner ear, resulting in multiple recurrent short episodes of dizziness or vertigo, imbalance, and nausea provoked by specific head movements.

Because most cases of BPPV are from debris in the posterior semicircular canals, symptoms are generally provoked by rolling over in bed, looking  up (“top shelf vertigo”),  getting a hair wash, yoga positions etc.

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BPPV can be caused by head trauma, vestibular neuronitis, or posterior head positioning during dental work, hair washing or neck manipulation, but can also occur spontaneously.

The diagnosis of BPPV can be suggested by history, but is confirmed by a provocative test such as the Hallpike-Dix maneuver.   In this test, a person is brought from sitting to a supine position, with the head turned 45 degrees to one side and extended about 20 degrees backward. A positive Hallpike-Dix test consists of a self-limited episode of vertigo accompanied by abnormal eye movements (nystagmus) that comes on after a short latency period. The symptoms will often recur when the patient is brought back up to the sitting position, but after that will quickly fatigue.

The nystagmus can be made more obvious by removing visual fixation using Frenzel lenses:

Untreated, symptoms of BPPV can persist for a few weeks or months, then stop spontaneously, but will often come back again.  Affected patients will try to avoid provoking dizziness by sleeping with two or more pillows at night, not sleeping on the “bad” side, and modifying their daily activities so as to avoid head positions that exacerbate symptoms.

However, once correctly diagnosed, BPPV can be readily treated by simple maneuvers that can be performed in a doctor’s office, such as the Epley maneuver:

The Epley can be very effective, with an 80% cure rate, particularly when followed by the these precautions to reduce the chance that debris might fall back into the sensitive back part of the ear:
1. Have the patient sleep semi-recumbent for the next 2 nights in a recliner chair
2. Encourage them to avoid tilting the head backwards for the next 2-3 days – do not go to the hairdresser or dentist, avoid putting the head back for shaving, accessing the top shelf or putting in contact lenses etc.  It is sometimes helpful to have the patient wear a soft cervical collar to remind them of this restriction.
3. If the symptoms recur when normal activity is resumed, the patient should undergo at least one further trial of the Epley maneuver.

If the patient cannot get to a doctor familiar with the Epley, they can try a home exercise such as the Brandt-Daroff exercises.  These exercises take longer to work, but many patients get significant relief of their symptoms within 7-10 days.

Download Brandt-Daroff Exercise Instructions Here

If the patient has persistent symptoms despite multiple attempts at the Epley and/or Brandt-Daroff exercise, one should first consider an alternate explanation for paroxysmal vertigo such as basilar migraine, acoustic neuroma, “Tournado” epilepsy or Meniere’s disease.  However, if the diagnosis of BPPV seems secure, and symptoms are truly recalcitrant, there are surgical options such as posterior canal plugging.

Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN) with conduction block is an acquired immune-mediated demyelinating neuropathy, which causes slowly progressive weakness, fasciculations, and cramping. It can resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but distinction is important since MMN usually improves with immunosuppressive treatment.

MMN is more common in men than women with a mean age at onset of 40 years (range of 20–70). The most common initial symptoms are wrist drop, grip weakness, and foot drop. Weakness progresses asymmetrically, but usually remains more prominent in the arms than in the legs. Weakness is typically more pronounced than would be suggested by the degree of muscle atrophy present. Affected patients also complain of muscle cramps and fasciculations. Tendon reflexes are reduced in affected regions. Sensory complaints are unusual.

These symptoms and signs from MMN are very similar to those seen in early ALS, and many patients are initially misdiagnosed with this disorder. MMN can usually be distinguished from ALS by its more slowly progressive disease course, the absence of upper-motor-neuron signs such as spasticity and hyperreflexia and the lack of difficulty with speech and swallowing.

However a carefully planned and executed electrodiagnostic study (EMG) is critical for distinguishing these disorders. MMN is a demyelinating neuropathy, while ALS is an anterior horn cell (motor neuronopathy) which causes secondary axonal degeneration of the motor nerve. When one suspects MMN clinically, identifying partial motor conduction block is critical in confirming the diagnosis.

The presence of high titers of antibodies to GM1 ganglioside can also be useful for confirming the diagnosis of MMN, but are only present in 20-60% of patients, and are rarely present in ALS patients, underscoring the importance of clinical suspicion and the EMG for making the diagnosis.

MMN is an immune mediated disorder and strength can recover after  repeated treatments with intravenous immunoglobulin (IVIG), whereas ALS does not respond to this or any other treatment, hence the importance of distinguishing these 2 disorders:

Disease                                                           MMN                                           ALS
Distribution of weakness                        Asymmetric,Arms                Ultimately generalized
Upper motor neuron findings                 Absent                                   Usually present
EMG                                                        Conduction block                   Motor axonal loss
Anti GM1 Ab                                               20-60%                                  10%
Response to IVIG                                       Yes                                           No

The clinical pictures below are from a patient with longstanding generalized weakness that I encountered several years ago.  The first picture shows his severe upper  limb atrophy (and weakness):

MMN pre

His EMG showed conduction block, suggesting MMN:


And the second picture showed the clinical improvement that had already occurred after 6 monthly treatments with IVIG:

MMN post

Obviously it is important to at least consider this treatable disorder in all patients with suspected ALS or motor neuron disease, and it is very important to see a neurology specialist with additional training and certification in neuromuscular medicine and/or electrodiagnostic medicine. Click here or call 732 923-5576 to find out more about the Central Jersey MDA and Neuromuscular Center at the Monmouth Neuroscience Institute.