Monthly Archives: October 2009

A Korean medical journal recently published a neat little article on a single patient with the clinical diagnosis of PSP. Photos were taken of this gentleman over a four-year period (age 62, age 62, and age 66). There’s also a photo of this gentleman’s eyes when he was in his 40s. The photos show his eyes before the onset of ocular symptoms and after. Some MRI images are included as well. The full article is available for free online. I’ve copied the abstract and some excerpts below.
Robin

Journal of Korean Medical Science. 2009 Oct;24(5):982-4. Epub 2009 Sep 24.

Exodeviated ophthalmoplegia in a patient with progressive supranuclear palsy.

Kim C, Lee HW, Park MY.
Department of Neurology, Han Family Hospital, Daegu, Korea.

We report a patient with progressive supranuclear palsy (PSP) with his serial photographs before the onset of ocular symptoms and after the onset with two year intervals. These photographs show his progressive eyeball deviations toward complete exotropia. There were no effective voluntary eyeball movements, Bell’s phenomenon, doll’s eye movements, and vestibulo-ocular reflexes. These signs indicate the involvement of the oculomotor nuclear complex by the disease. We suggest that PSP may cause not only ‘supranuclear’ but also ‘nuclear’ complete ophthalmoplegia with exodeviation of the eyes.

PubMed ID#: 19795006

Here’s a link to the full article (available online for free) and some excerpts:

http://www.pubmedcentral.nih.gov/articl … d=19795006

Introduction
“Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by progressive dystonic axial rigidity, postural instability, pseudobulbar palsy, subcortical dementia, and impaired of voluntary eye movements. Facial appearances are characteristic in PSP. The patients usually show a fixed ‘surprised’ stare, retracted head, raised eyebrows, markedly decreased blinks (less than 4 per min), and progressive downward gaze palsy. Previously, only a few reports describe PSP patients with photographs. We report a probable PSP patient with progressive eyeball deviations which was documented with serial photographs.”

Case Report
“A 66-yr-old man was admitted because of dysphagia with repeated aspirations in March 2007. In October 2003, he was evaluated in a hospital because of blurred vision, dislike of bright lights and easy falls. He remembered several episodes of falling while riding a motorcycle since 2000. These episodes were not associated with feelings of dizziness or faintness and were independent of specific situation or body position. He visited several local eye clinics where he was diagnosed with bilateral cataracts and presbyopia, and underwent bilateral lens implantation in 2000. He did not benefit from the surgery, but felt a progressive worsening toward imbalance and unsteadiness when walking. Eye evaluation, in October 2003, revealed bilateral surgical pseudophakias and moderate exodeviation. Pupils were irregularly shaped and direct light reflexes were sluggish bilaterally. Fundoscopic examinations showed mildly increased cup to disk ratio (0.6 OD and 0.7 OS) with peripapillary atrophy in both eyes. Vertical ocular movements for willed gaze as well as following objects were slow and limited, though full ocular movements were elicited during passive head motions. Volitional horizontal gaze and pursuit of a visual target were also slow with bilateral adduction paresis. However, convergence was normal. Goldmann visual fields were also normal. He was slow and made errors when performing distal rapid alternating movements. He tended to topple backwards. There was neither resting nor action tremor. He was diagnosed with ‘parkinsonism’ and treated with levodopa/benserazide and other dopamine agonists, but his symptoms did not improve. His illness progressively worsened thereafter. He experienced frequent falls and needed a cane to walk. His head was retracted, and his voice was reduced to a slurred growl. He became unable to look down and had difficulties in swallowing. In November 2006 and January 2007, he suffered from aspiration pneumonias, and underwent tracheostomy and gastrostomy. Magnetic resonance imaging of the brain demonstrated moderate atrophy of the whole cerebrum and brainstem, as well as mild bihippocampal atrophy.”

“He was admitted to our hospital in March 2007. His medical history was otherwise unremarkable. His previous medications included levodopa/carbidopa, ropinirole, selegiline, and afloqualone. His family history was negative for gait, cognitive, or other neurological disorders. He responded correctly to simple verbal commands. His eyes deviated up and lateral, and his vertical and medial eye movements were absent. When the patient attempted to look laterally, only brisk quick lateral eyeball movements were observed on the same side, but the opposite eye showed no movement at all medially. He could not converge his eyes. There was neither Bell’s phenomenon nor optokinetic nystagmus. Caloric stimulations with both warm and cold water did not evoke any nystagmus bilaterally. Doll’s eye maneuver did not evoke any eyeball movements at all. However, because of the patient’s severe nuchal rigidity and retrocollis, the examination was suboptimal. He could not sit in bed by himself, and he repeatedly fell backward without support. His axial rigidity made his distal limb movements appear ataxic but when reaching for close objects with his back supported, his ataxic movements decreased markedly. Reflexes were symmetrical and minimally brisk in the upper and lower extremities with bilateral flexor plantar responses. There was no resting tremor.”

Discussion
“Among the earliest signs of PSP is supranuclear gaze palsy. It includes slowing of voluntary downward saccades, a high percentage of errors in the antisaccade task, and frequent presence of square-wave jerks, and progression to a complete vertical gaze palsy. The doll’s head maneuver may generate a normal vertical vestibular-ocular response that demonstrates the integrity of the third nerve nuclei and confirms that the eye movement disorder is supranuclear. Internuclear ophthalmoplegia (INO), which is an adduction paresis on conjugate horizontal gaze (usually with abduction nystagmus of the contralateral eye), has been described previously in an apparently milder form in a series of 4 patients with PSP.”

“In our case, we could not elicit any effective eyeball movements in his eyes. From the patient’s serial photographs, it is evident that his ophthalmoplegia had been accompanied by progressive eyeball deviation in the upward and outward directions.”

“We suggest that the earliest ocular findings in PSP may be supranuclear gaze palsy, but as the disease progresses, nuclear level gaze control may also be affected, and exodeviation of the eyeballs may be a clinical manifestation in advanced PSP patients.”

I stumbled across this 2007 medical journal article this week when someone in Texas (whose mother has a clinical diagnosis of PSP) asked me to evaluate whether the University of Texas Southwestern would be a good brain bank to donate her mother’s brain. (Answer: No.)

This is a case report of a 35-year-old woman who died due to neuroleptic malignant syndrome, caused by Haldol (an antipsychotic). Upon brain autopsy, it was discovered this woman had PSP.

I find this article timely because this morning I heard that an Arizona-based woman with CBD was given Haldol by hospice and reacted badly to the medication. (The term NMS wasn’t used.) Note that Haldol is common included in hospice medication kits given to families for emergencies. And I heard last week of a local person with Parkinson’s Disease who died after being given Haldol in the hospital.

Here’s my layperson soapbox… Why Haldol is given at all to anyone is beyond me. But why it’s given to those with parkinsonism symptoms or the elderly with dementia is really hard to fathom. (There’s an FDA black-box warning on all antipsychotics for the elderly with dementia.) The information about Haldol in particular is readily available in language that laypeople can understand. Speak with your MD! Many in the Lewy Body Dementia group avoid the administration of Haldol in emergency situations by reporting in patient records (and on MedicAlert bracelets) that family members are allergic to Haldol.

The abstract of the March 2007 article is copied below along with extensive excerpts. (You can see from the first sentence of this excerpt that this woman had very bad luck.)

Robin

American Journal of Forensic Medicine & Pathology. 2007 Mar;28(1):59-62.

Undiagnosed progressive supranuclear palsy in a patient with neuroleptic malignant syndrome due to use of neuroleptics: the
utility of autopsy in deaths due to known drug reactions.

Kemp WL, Fitzgerald J, White CL 3rd.
Department of Pathology, Division of Forensic and Autopsy Pathology, University of Texas Southwestern at Dallas, Texas.

Medical examiners must decide whether or not a complete autopsy is warranted in evaluation of deaths that have been referred to their
office. This decision is influenced by many factors. In most cases, the choice to perform only an external examination occurs in deaths where the decedent had previously documented potentially lethal natural disease or well-documented trauma. We report a patient who apparently died of the sequelae of a well-known complication of pharmacotherapy (neuroleptic malignant syndrome following Haldol administration). The death was referred to the medical examiner’s office, where, based upon the history, an external examination was performed. Subsequently, the family requested an autopsy by the treating hospital. The autopsy established the diagnosis of progressive supranuclear palsy (PSP). The patient’s presenting signs and symptoms were not typical of the disease; however, PSP most likely played a role in the neuroleptic malignant syndrome-like manifestations the patient exhibited following the Haldol administration. The results of the complete autopsy highlight its importance in identifying and enhancing our understanding of the underlying conditions in natural disease-based causes of death involving known therapeutic complications.

PubMed ID#: 17325467 (see pubmed.gov for abstract only)

Excerpts:

Case Report
“This 35-year-old woman with Staphylococcus aureus osteomyelitis occurring after an injury of the finger sustained while cooking was admitted for a partial amputation of the digit after failing outpatient antibiotic therapy. Her past medical history was remarkable for hypertension, obesity, hypoventilation syndrome, schizoaffective disorder, and a progressive but ill-defined movement disorder of 2 years duration that was felt to represent akathisia or tardive dyskinesia. The patient also exhibited progressive apathy, which
was attributed to her underlying psychiatric disorder and use of major tranquilizers. Notably, there was no history of frequent falls. Baseline medications included quetiapine (Seroquel) and sertraline (Zoloft).”

“Following surgery, she was noted to have frequent writhing movements involving her arms and shoulders, without lip-smacking or tongue protrusion. Antipsychotics and benzodiazepines were administered in increasing doses over several days, with no decrease in choreoathetosis. Two weeks into her hospital stay, the patient developed an acute delirium associated with dyspnea, tachycardia, hypertension, and fever (39.5°C). Within hours, she became profoundly hypotensive, necessitating aggressive fluid and pressor support. She developed disseminated intravascular coagulation, rhabdomyolysis, acute renal and hepatic failure, brain infarcts, and a non–ST-segment-elevation myocardial infarct. Although the patient did not manifest increased muscle tone, a diagnosis of NMS was
made and she was treated. A seizure disorder was ruled out with an electroencephalogram (EEG). Cultures were unrevealing,
and no source of sepsis could be identified. The psychiatric service was consulted and opined that she might have catatonic agitation or a conversion disorder. After recovering from multisystem organ failure, the patient was transferred to a nursing home for long-term care. She experienced additional complications, including aspiration pneumonia, and expired a month after discharge from the hospital. Because of the history of trauma inducing the osteomyelitis, her death was referred to the medical examiner’s office. At the
time of her evaluation, an external examination only was performed, and the cause of death ruled as complications of schizoaffective
disorder, with osteomyelitis with right finger amputation being listed as a significant contributory condition.”

“An autopsy was subsequently performed by the treating hospital at the family’s request. … These histologic features are consistent
with a diagnosis of progressive supranuclear palsy (PSP).

Discussion
“PSP is a neurodegenerative hypokinetic movement disorder. Patients usually present later in life (around 50–70 years of age) and characteristically have parkinsonism (rigidity, slowed movements, and tremor) and abnormal eye movements (supranuclear gaze palsy). Patients also commonly have postural instability and present with falls. However, as the areas affected within the brain are heterogeneous, the clinical features may be variable. Other features can include dysarthria, dysphagia, cognitive changes, and aphasia. Although the classic clinical finding is supranuclear ophthalmoplegia, many patients may not manifest this symptom until
late in the course of the disease or, in some cases, not at all. One percent to 8% of patients diagnosed with Parkinson disease clinically are found to have PSP, and some patients diagnosed with dementia are found to have PSP. Apathy, anxiety, disinhibition, and dysphoria are also commonly associated symptoms, and abnormal motor behaviors, including chorea and limb dystonia, are sometimes present. In this case, it is possible that the patient’s progressively worsening choreoathetosis and mood disturbances were caused by PSP, rather than a true schizoaffective disorder and the associated neuroleptic treatment (tardive dyskinesia).”

“The underlying pathologic mechanism of PSP is hyperphosphorylation of tau. Importantly, patients with PSP potentially have multiple neurotransmitter abnormalities, including those affecting dopamine, acetylcholine, Y-aminobutyric acid, and norepinephrine.”

“NMS is a rare adverse reaction (0.2% of patients) associated with the use of neuroleptics (including atypicals such as olanzapine), some nonneuroleptic medications such as tricyclic antidepressants, and following the rapid withdrawal of antiparkinson medications (including levodopa). The proposed mechanism of NMS is widespread block of dopaminergic activity in the brain. The diagnostic criteria for NMS are not agreed upon, but the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) requires severe muscle rigidity and elevated temperature and 2 of the following: diaphoresis, dysphagia, tremor, incontinence, changes in consciousness, mutism, tachycardia, elevated or labile blood pressure, leukocytosis, and laboratory evidence of muscle injury. However, the literature includes reports of patients presenting with other than the classic symptoms, and one paper reports that less than 50% of cases manifest classic symptoms. The symptoms may be related to which portion of the dopaminergic system is most prominently involved, with nigrostriatal involvement causing rigidity and temperature elevation, mesocortical involvement causing changes in mental status, and tuberoinfundibular involvement causing temperature dysregulation. As hinted at above, patients with Parkinson disease are at increased risk for the development of NMS. NMS has also been described in Shy-Drager syndrome, olivopontocerebellar atrophy, and multisystem atrophy. One paper in the literature reports a case in which a patient with pure akinesia developed hyperthermia, muscle rigidity, abnormal blood pressure, and elevated muscle-derived serum enzymes, which was considered to be NMS. Autopsy revealed the patient to have PSP.”

“While the patient presented in this case report did not fit the demographics or have the clinical symptoms normally associated with PSP, her pathologic features were consistent with the disease. Also, outside of 1 reported case, PSP per se has not often been associated with the increased risk of development of NMS, though clinical parkinsonism has, both in patients receiving antiparkinson medication and in those receiving antipsychotics, such as Haldol. As patients with PSP have abnormalities in the dopaminergic system, it seems reasonable to suggest that patients with this disease have an increased risk for the development of NMS. Indeed, the difficulties in distinguishing PSP from other causes of Parkinsonism clinically raise the possibility that some patients with Parkinsonism who develop NMS may, in fact, have PSP or some other cause of movement disorder besides idiopathic (Lewy body) Parkinson disease.”

“In conclusion, this case illustrates the importance of the autopsy even in patients with known, well-reported reactions to medications. This patient most likely manifested a form of NMS after exposure to neuroleptics in the treatment of her psychiatric condition; however, the patient’s underlying PSP likely increased the risk of its development. As is evident from this case, the discovery of an underlying disease process which may have helped precipitate the observed reaction can have importance for the treating physician and hospital, as well as the correct certification of the cause of death.”