Movement disorders emergencies involve a large number of patients ranging from those with primary and secondary movement disorders to those with psychiatric histories on medications. As many of these patients receive their treatment on an outpatient basis, emergencies involving these conditions introduce a new layer of complexity. Of the many emergencies seen in the category of movement disorders, the topics covered in this chapter are parkinsonism-hyperpyrexia syndrome, neuroleptic malignant syndrome, serotonin syndrome, acute dystonic reaction and dystonic storm, and malignant catatonia. The following patient vignettes will serve as introductions to each topic.
CASE 17-1
A 74-year-old woman with Parkinson disease (PD) and dementia was admitted to the ward with falls and failure to thrive. At home, she was taking carbidopa/levodopa 25/100 mg 1.5 tablets 6 times a day as well as rasagiline 1 mg daily. In the hospital, the patient became agitated and refused to take her medications at most scheduled administration times. Over the next 2 days, she became less agitated but was extremely rigid and immobile. During these times she took her medications; however, once she took carbidopa/levodopa more regularly, she again became agitated and refused her medications. She again became rigid and then was nonverbal, not following requests, and appeared at risk for aspiration as food sat in her mouth and there was limited swallowing. She developed large fluctuations in blood pressure and then developed a low-grade fever with elevated WBCs as well as an elevated creatine kinase (CK). Her infectious workup was negative.
She had a nasogastric tube placed, and levodopa was reintroduced. A diagnosis of parkinsonism-hyperpyrexia syndrome was made. The patient slowly became less rigid, and her agitation was managed by inpatient psychiatry. Her fevers remitted, and the severity of her BP fluctuations reduced. Her CK and WBCs returned to normal.
CASE 17-21
A 67-year-old man with an 8-year history of PD was admitted with an episode of collapse at home. He was found to have postural hypotension and nitrite-positive urine dip. The labile blood pressure was thought to be caused by his anti-parkinsonian medications (4 mg ropinirole once a day, 25/100 mg carbidopa/levodopa 5 times a day, and 10 mg selegiline once a day). While in hospital, the ropinirole was titrated off in 3 days. The urinary tract infection was treated with trimethoprim. Three days post-admission, the patient was found in a “confused, rigid, and hallucinating” state with a temperature of 40.2 C (104.4 F). He had increased tremor and stiffness, profuse sweating, tachypnea, and tachycardia. The patient had been compliant with the rest of his medications.
A diagnosis of parkinsonism-hyperpyrexia syndrome was made. He was cooled via external ice packs and cold intravenous saline. A nasogastric tube was inserted, an additional dose of his usual Levodopa was given, and ropinirole was restarted. The creatine kinase was 845 U/L (50–200 U/L), and urine showed blood on dipstick. The patient started recovering over the next few hours, and his muscle tone and temperature returned to baseline over the next few days.
CASE 17-32
A 58-year-old woman developed her first PD symptoms in 1984, after which selegiline was prescribed; a year later, levodopa was added. She began to experience wearing off phenomena in which she had foot dystonia, leading to the initiation of bromocriptine. Her condition progressed to the point that she had motor fluctuations, dyskinesia of the legs and trunk, as well as severe, painful off periods by 2003. At that point she was on a total of 1500 mg of levodopa, 8 mg of pramipexole, and 300 mg of amantadine daily. She was a surgical candidate and had DBS electrodes implanted in both subthalamic nuclei (STN).
As instructed, she had been off of her medications the night before surgery. After the surgery, she had carbidopa-levodopa reintroduced at a lower dose (250 mg twice a day) as she had some lesioning effect from the surgery and the DBS was left on. The next day, she was febrile with a temperature of 39.8°C, confused, with dramatic alterations in blood pressure, tachypnea, and tachycardia. Her PD medications were slowly reintroduced, but at lower dosages compared to presurgery and she slowly improved. She had been noted to have an elevated white blood cell count and creatinine kinase (CK) that resolved over time. Her infectious workup was negative but had been empirically treated for infection. She had returned back to normal consciousness. Two months later, she had a similar series of events after stopping antiparkinsonian medications for 18 hours during a period of confusion. Her CK value was three times normal, and she had unsuccessful treatment with antibiotics, supportive care, and antiparkinsonian medications. It was not until dantrolene (25 mg/8 h) was administered that there was a reversal of symptoms within a few hours.
Parkinsonism-hyperpyrexia syndrome is a condition that is characterized by fever, altered mentation, autonomic dysfunction, muscle rigidity, and elevated serum CK levels, and is potentially fatal if not recognized and treated. Its symptoms mirror those of neuroleptic malignant syndrome; however, it is seen in the scenario of withdrawal of dopaminergic medications. The fever is due to possible vasodilation impaired in PD resulting in hyperpyrexia.3
It was first described in a case report published in 1981 regarding a patient who had stopped her levodopa approximately 1 week prior to presenting to the emergency department (ED) with neuroleptic malignant-like symptoms. After being treated with hydration and antibiotics without effect, reintroduction of her levodopa led to improvement.4 The importance of recognizing its symptoms was demonstrated in a case of a man who had altered mental status who had his levodopa discontinued. By the time the diagnosis was made, the patient had developed renal and respiratory failure and he expired despite trying to reintroduce the medication.5
Many cases give specific example of levodopa withdrawal; however, dopamine agonist withdrawal has also been implicated. In patient 2 introduced above, the patient had been thought to have labile blood pressure secondary to ropinirole administration, so the medication was tapered over 3 days while maintaining his levodopa therapy. A parkinsonism-hyperpyrexia syndrome developed, and the patient was given extra levodopa while reintroducing the ropinirole, leading to resolution of his symptoms.
As mentioned in Case 17-3, another precipitator of abrupt levodopa withdrawal resulting in parkinsonism-hyperpyrexia syndrome is at the time DBS is placed. In patients with DBS, it may be necessary to slowly activate the DBS while tapering medication. There has also been debate as to the rate of withdrawal of levodopa after introduction of DBS. Some believe that symptomatic improvement from DBS can lead to a 30% reduction in levodopa, while others feel that levodopa can be discontinued all together.2,7–9
After initial evaluation, the immediate steps to be taken begin with reintroduction of the dopaminergic medication. If there is an issue of dysphagia, it may be necessary to place a nasogastric (NG) tube or a percutaneous endoscopic gastrostomy (PEG) tube in those who chronically have dysphagia problems. In addition, in those who use newer therapies that introduce a more continuous infusion of levodopa, issues such as tube obstruction or pump failure may require the reintroduction of oral therapy. Other modes of introduction such as transdermal patches may also be necessary.
Other options of intervention have also been utilized. A neuroleptic malignant syndrome (NMS) research group has indicated the efficacy of using dantrolene 80 mg three times daily as has been seen to be helpful in malignant syndromes in general. They also mentioned using bromocriptine 5–10 mg three times daily, as it appears to be efficacious for malignant syndrome.10 There have also been data indicating that steroid pulse therapy (1 g daily) is useful in malignant syndrome in PD for reducing the illness duration and improving symptoms.11
In addition to reintroducing dopamine treatment, multiorgan system management may be necessary. Depending on the current status of the patient, an intensive care unit may need to be utilized. Treating supportively for the fevers, rehydration, and being watchful/treating for renal and respiratory failure are important. During this support, an infectious workup should be ensued to rule out any other or contributing causes of the patient’s symptoms. Some PD patients can be more predisposed to developing disseminated intravascular coagulation and anticoagulation can be recommended in those patients.
CASE 17-412
A 48-year-old man was brought to the emergency department (ED) because of intoxication. The patient was in respiratory distress and intubated for airway protection. During his hospitalization, haloperidol 5 mg intravenously every 6 h was given and titrated up to a dose of 60 mg per day over 5 days for delirium. On hospital day 18, his temperature peaked to 107.1°F, and he began to experience alerted mentation, rigidity, and autonomic dysfunction. Neuroleptic malignant syndrome (NMS) associated with haloperidol was suspected, as no other causes for these symptoms were present. A diagnosis of NMS was entertained, and once haloperidol was discontinued and the patient was given dantrolene and bromocriptine, his symptoms began to resolve.
CASE 17-513
A 67-year-old woman was admitted to be evaluated for dementia with 6 years of progressive memory loss. Her increasing confusion and agitation required medical management with haloperidol, 1 mg at bedtime for approximately the last 5 months. In addition, a continuous “pill-rolling” tremor had developed over the past several weeks. On initial examination, the patient was afebrile and her blood pressure was 120/86 mmHg.
The initial impression was that of parkinsonism, idiopathic versus drug-induced. Upon admission, the patient had increasing agitation and required additional haloperidol. On hospital day 1 she received 12 mg total followed by an additional 13 mg over the next 48 hours. On hospital day 4, she was found by nursing staff to be minimally responsive, rigid, and incontinent, with a temperature of 40.5°C (104.9°F). Her blood pressure was 80/50 mmHg, and her pulse rate was 154 per minute. She was started on antibiotics and transferred to the ICU. Her infectious workup was negative. She had an elevated leukocyte count of 19,000/mm3, and a CK level of 2,381 U/L. Head computed tomography (CT) and abdominal ultrasonography were negative. She was started on inotropic support. On the following day, the fever rapidly subsided to 38.4°C (100.1°F) and the CK value declined to 1691 U/L. Her fever subsided, and she no longer needed antibiotics or iontropic support. On the ninth hospital day, her urine output deteriorated, causing concern about acute renal failure. Her temperature was 37.2°C (99.0°F). A urinalysis showed 30–40 leukocytes and 10–20 erythrocytes per high-power field, and she was treated for a urinary tract infection.
She was placed on a regimen of carbidopa/levodopa 10/100 three times a day, and her tremor rapidly improved. A psychiatric consultation was obtained regarding continuing medication use for future agitation. Based on the hospital course, this case was felt to represent the neuroleptic malignant syndrome, and it was suggested that lorazepam 1 mg, taken orally three times a day as necessary, could be substituted for haloperidol in case of agitation.
NMS is a constellation of symptoms that include hyperthermia, significant rigidity, altered mental status, and autonomic instability. Workup usually finds an elevated serum CK level. NMS is brought upon by exposure to neuroleptics, which leads to its differentiation from malignant catatonia (described later this chapter). A 1980 review defined this set of symptoms that had been recognized since the 1960s.14 Through the years, the exact criteria for NMS was highly debated but in 2011, the consensus was formed on making diagnosis by the Delphi method.15
The syndrome was initially described after exposure to haloperidol; however, there are a variety of neuroleptic medications that can lead to this condition through dopamine receptor blockade (see Table 17-1).16,17 Also important to note, dopamine-blocking antiemetics can cause NMS.
Medications That Can Cause Neuroleptic Malignant Syndrome
| Typical Antipsychotics | |
| Chlorpromazine | Pimozide |
| Fluphenazine | Perphenazine |
| Haloperidol | Promazine |
| Loxapine | Thioridazine |
| Molindone | Thiothixene |
| Levomepromazine | Trifluoperazine |
| Atypical antipsychotics | |
| Aripiprazole | Paliperidone |
| Clozapine | Quetiapine |
| Iloperidone | Risperidone |
| Lurasidone | Ziprasidone |
| Olanzapine | |
| Antiemetics | |
| Domperidone | Prochlorperazine (also typical antipsychotic) |
| Droperidol (also typical antipsychotic) | Promethazine |
| Metoclopramide (rather than Metaclopramide) | |
In addition, with the advent of longer-acting neuroleptics in the form of depot injections such as haldoldecoanate, longer-duration malignant syndromes have been seen. One case of a 38-year-old who developed NMS after receiving multiple maintenance doses of a haldol decanoate proved to be extremely difficult to control with multiple crises during his therapy.18
It is sometimes very difficult to differentiate NMS from serotonin syndrome and malignant catatonia without a sufficient history, even more so in a patient with altered mental status. GI symptoms such as nausea and vomiting, as well as myoclonus, can be indicators to differentiate serotonin syndrome from NMS.19 Malignant catatonia can be seen in the patient not currently on any antipsychotic therapy.
For patients presenting with NMS, the first and most important step of treatment after going through a differential is removal of the offending medication. These patients should be closely monitored in an ICU setting to provide maximal therapeutic and supportive care. For mild cases of NMS, benzodiazepines may be beneficial for catatonic symptoms.20 Dopaminergics such as bromocriptine, levodopa, rotigotine, apomorphine, and amantadine have also been used, which treat the parkinsonian symptoms.21 Dantrolene is used as a muscle relaxant. For bromocriptine and dantrolene, these should be used for at least 10 days following resolution of NMS symptoms to prevent recurrence. As mentioned above, in the case of long-acting injectable depot medications, close observation for a longer duration and treatment of the patient are needed until a sufficient number of half-lives of the medication have passed. In cases of medically refractive NMS, another option is electroconvulsive therapy.
CASE 17-622
A 55-year-old man with a history of attention-deficit hyperactivity disorder (ADHD), major depression, anxiety, and hematuria presented to the ED 16 hours after ingesting approximately 180 25-mg tablets of controlled-release paroxetine and an unknown quantity of immediate-release paroxetine. The patient attempted suicide after the loss of his job. On initial presentation, the patient’s vital signs were within normal limits. He was initially asymptomatic, but progressively worsened with symptoms of diaphoresis, mydriasis, confusion, hyperreflexia, hypertonia, clonus, hyperactive bowel sounds, and diarrhea. His admission workup included urine and serum toxicology screens, routine chemistries and blood counts, hepatic function, CK, and urinalysis, all of which were unremarkable. A mildly prolonged QT interval was present on admission.
As the patient likely had serotonin syndrome, he was started on intravenous (iv) lorazepam and cyproheptadine at a dose of 4 mg every 8 hours. Three days after admission, the patient remained tremulous, hyperreflexic with clonus, and oriented only to self, with poor attention and slurred speech, so cyproheptadine was increased to 8 mg every 6 hours. ECGs continued to show a prolonged QT interval. CT was unremarkable. EEG was consistent with encephalopathy. LP showed mildly elevated protein content, but was otherwise negative. Thyroid function was within normal limits.
On hospital day 4, the patient’s vital signs became unstable, and he was febrile to 38.3 C (101 F). His CK peaked at 4052 U/Land he was transferred to the intensive care unit. He had subtle infiltrates on chest X-ray and was treated for aspiration pneumonia with antibiotics. He had an elevated white blood count and required ventilation for 2 days. He was extubated; however, on the 9 th day after the overdose, the patient was found pulseless and did not respond to multiple rounds of advanced cardiac life support. The cause of death was due to a massive pulmonary embolism.
Serotonin syndrome is a constellation of symptoms that includes alteration of mental status, neuromuscular hyperactivity, and autonomic instability. There are multiple causes of elevated serotonin levels in the body, which include overdose of medication, interactions between medications, or the effects of the medications alone. As described in previous reviews, the severity of the syndrome can vary greatly, with additional factors designating the level. In mild cases, the syndrome includes a feeling of discomfort and abnormal movements. The syndrome becomes moderate in severity with inclusion of fever and alteration in mental status, and severe cases include more dramatic systemic signs, including muscle breakdown, seizure, and renal and respiratory failure.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
