Karen Frei

• Medical Doctor at Loma Linda University

A comprehensive and multidisciplinary guide to understanding and treating a wide range of movement disorders, including parkinsonisms, tremor, tics, dystonia, chorea, ballism and myoclonus. Split into five sections, the first is a basic introduction to the subject, covering the principles of human motor behavior and functional anatomy. The next thr...

Background Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This st...

Cervical dystonia (CD) is an idiopathic focal dystonia characterized by abnormal head and neck posture caused by tonic involuntary contractions in a set of cervical muscles. Four subtypes, based on the principal direction of posture, consist of: • - Torticollis: Rotation of the head left or right in the transverse plane. • - Lateralcollis: Head ti...

Levodopa is the most effective drug for treating the motor symptoms of Parkinson’s disease. It is usually combined with a dopa-decarboxylase inhibitor to extend its half-life increasing levodopa availability to the brain. In patients who are younger and present with milder symptoms, medications such as dopamine agonists, catechol-O-methyl transfera...

Tremor is one of the most common movement disorders, though it can arise in the context of several unrelated neurological disorders whose pharmacology and anatomical origins differ greatly. Treatment of tremors can take advantage of several medications and neurosurgical treatments. Medications useful for treating tremor are discussed in this review...

Smooth pursuit eye movement (SPEM) abnormalities are commonly seen in Parkinson’s disease (PD). Both reduced speed and saccades seen during SPEM, also known as saccadic pursuit (SP), have been studied in PD. A comprehensive literature review analyzed 26 studies of SPEM and PD. It appears that a greater proportion of PD patients have SPEM abnormalit...

Tardive syndromes (TDS) are a group of hyperkinetic and hypokinetic movement disorders that occurs after exposure to dopamine receptor blocking agents such as antipsychotic and antiemetic drugs. The Abnormal Involuntary Movement Scale (AIMS) is a widely used instrument that has become the standard for assessment of tardive dyskinesia (TDD), the mos...

Tardive dyskinesia (TD) is a potentially permanent movement disorder resulting from chronic use of dopamine receptor blocking agents (DRBA). Identified risk factors include the type of antipsychotic agent, being greater for those of first generation antipsychotics (FGA), the duration of illness and cumulative dose of DRBA and advanced age. Female s...

We propose the use of the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements and the analogous repetitive movements of the limbs, trunk, or pelvis. The term tardive syndrome is an umbrella term to be used to refer to the spectrum of all persistent hyperkinetic, hypokinetic, and...

Symptoms of Parkinson’s disease have been controlled with levodopa for many years; however, motor complications consisting of wearing off of medication effect and dyskinesias tend to occur within a few years of starting levodopa. Motor complications can begin a few months after taking levodopa, with the average time to onset estimated to be 6.5 yea...

Cambridge Core - Neurology and Clinical Neuroscience - Treatment of Dystonia - edited by Dirk Dressler

Since the original description of side effects of neuroleptics, different terminologies and definitions for tardive dyskinesia (TD) and tardive syndrome (TS) have been used by different authors, and often these two terms have been used interchangeably. This paper proposes a nosology designed to define and clarify various terms and phenomenologies w...

In most cases the cause for dystonia is unknown. In a small number of patients, trauma precedes the onset of the dystonia. Significant head trauma is a well-recognized precipitating factor in dystonia. However, it has become increasingly recognized that peripheral trauma can also result in dystonia. Secondary dystonia resulting from both central an...

Ever since botulinum toxin was first used as a treatment for strabismus in 1980, it has become instrumental in the treatment of a myriad of conditions with focal muscle overactivity including cosmetic uses to treat wrinkles. Botulinum toxin use in the treatment of movement disorders including dystonia, hemifacial spasm, tremor, and tics is discusse...

Hallucinations and psychosis can be a part of Parkinson's disease and are considered to be a nonmotor symptom or a neuropsychiatric complication of the disease. Hallucinations of different modalities and delusions can occur beyond the common visual hallucinations. The various types of hallucinations and psychotic symptoms comprising the spectrum of...

Systematic Literature Review of Quetiapine for Hallucinosis/Psychosis in Parkinson’s Disease

Background: The aim was to elucidate clinical trial efficacy, safety, and dosing practices of abobotulinumtoxinA (ABO) treatment in adult patients with blepharospasm and hemifacial spasm. To date, most literature reviews for blepharospasm and hemifacial spasm have examined the effectiveness of all botulinum neurotoxin type A products as a class. H...

OBJECTIVE: To determine the minimum quantitative change on UPDRS that is detectable by PGIC and Clinician Global Impression of Improvement (CGI-I). BACKGROUND: Published data do not address the correlation between changes in Unified Parkinson’s Disease Rating Scale (UPDRS) score (quantitative) and Patients’ Global Impressions of Change (PGIC) ratin...

Geneva is home to the Red Cross and the United Nations, a fitting site for this international meeting. Emphasis was both on motor behavioral and behavioral motor disorders, including the physiology of behavior in Parkinson's disease (PD) and the phenotype of synucleinopathies, as also described in a textbook of the IAPRD published at the occasion o...

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P...

Importance Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.Objective To examine whether CoQ10 cou...

Fully updated throughout, the second edition of the Manual of Botulinum Toxin Therapy provides practical guidance on the use of Botox in a wide variety of disorders. New chapters have been added on the use of botulinum toxin in wound healing, in focal hand dystonia and in thoracic outlet syndrome, as well as others. There are new chapters on the us...

Fully updated throughout, the second edition of the Manual of Botulinum Toxin Therapy provides practical guidance on the use of Botox in a wide variety of disorders. New chapters have been added on the use of botulinum toxin in wound healing, in focal hand dystonia and in thoracic outlet syndrome, as well as others. There are new chapters on the us...

The vast majority of patients with primary dystonia are adults with focal or segmental distribution of involuntary movements. Although ∼10% of probands have at least one first- or second-degree relative to dystonia, large families suited for linkage analysis are exceptional. After excluding mutations in known primary dystonia genes (TOR1A, THAP1 an...

Sequence variants in coding and noncoding regions of THAP1 have been associated with primary dystonia. In this study, 1,446 Caucasian subjects with mainly adult-onset primary dystonia and 1,520 controls were genotyped for a variant located in the 5'-untranslated region of THAP1 (c.-237_236GA>TT). Minor allele frequencies were 62/2892 (2.14%) and 55...

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen f...

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen f...

This chapter attempts to describe the basics of genetics using selective neurological diseases as examples. Mutations can produce no change in the protein or they can produce an abnormal or truncated protein. Disease states can be caused by gene mutations, which are then passed on through to the next generation. Many disorders are inherited through...

Several interesting concepts regarding Parkinson's disease were recently presented at the XVIII World Congress on Parkinson's disease. The theory of alpha-synuclein acting as a prion, resulting in the spread of Parkinson's disease, was presented and related to the Braak hypothesis of neuropathology of Parkinson's disease. Nonmotor symptomatology of...

To evaluate the possible association of Parkinson disease (PD) and melanoma in North America. Thirty-one centers enrolled patients with idiopathic PD. At visit 1, a neurologist obtained a medical history. At visit 2, a dermatologist recorded melanoma risk factors, performed a whole-body examination, and performed a biopsy of lesions suggestive of m...

THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence...

The Manual of Botulinum Toxin Therapy provides practical guidance on the use of botulinum toxin in a wide variety of disorders, in many areas of medicine. Using clear line drawings, it describes the relevant injection sites for each condition and gives comparative dosage tables for the various formulations of toxin used in different muscle groups....

The Manual of Botulinum Toxin Therapy provides practical guidance on the use of botulinum toxin in a wide variety of disorders, in many areas of medicine. Using clear line drawings, it describes the relevant injection sites for each condition and gives comparative dosage tables for the various formulations of toxin used in different muscle groups....

Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some DeltaGAG mutation carriers present with late-onset focal dystonia...

Parkinson's disease is the second most common neurodegenerative disease following Alzheimer's disease. As there is no biomarker or diagnostic test available for the diagnosis of Parkinson's disease, diagnosis of this disorder can be challenging. Parkinson's disease symptoms include both motor and non-motor symptoms. Non-motor symptoms may require s...

Tremor is defined as involuntary rhythmic oscillation and is produced by muscle contractions. Hemifacial spasm is rapid involuntary muscle contractions on one side of the face in the distribution of the VIIth nerve. We present a severe case of hemifacial spasm that produces a head-nodding tremor-like movements.

The DeltaGAG deletion mutation in DYT1, causing a loss of a glutamic acid near the carboxyl terminus of torsinA protein (torsinADeltaE), is dominantly inherited and tends to result in a severe generalized form of dystonia with childhood onset. We have used a yeast two-hybrid interaction assay to examine torsinA and its mutant torsinADeltaE interact...

Hemifacial spasm (HFS) is characterized by involuntary irregular clonic or tonic movements of the muscles innervated by cranial nerve VII on one side of the face, and is most often a result of vascular compression of the facial nerve at the root exit zone (Muscle and Nerve 1998;21:1740). Disability associated with this disorder ranges from social e...

Background: Rasagiline (N-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). Objective: To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. Des...

We studied a case series of 9 patients with posttraumatic cervical dystonia, in whom involuntary muscle spasms and abnormal head postures occurred within 7 days after cervical injury. Patients were examined, treated with botulinum toxin as necessary, and were followed up to 5 years. Based on our observations of these cases, we propose that complex...

Background: Oral dopamine agonists are effective for treating early Parkinson's disease (PD). Rotigotine is a dopamine agonist delivered through a silicone-based transdermal patch that is replaced every 24 hours. Objectives: To assess the efficacy and safety of rotigotine in patients with PD not receiving dopaminergic medications. Design: Rand...

Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. To comprehensively characterize the clinical and genetic abnormalities of MLIV. Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returne...

Fabry disease is an X-linked inherited disorder resulting from a deficiency of alpha-galactosidase A. Cerebrovascular disease in Fabry disease includes small-vessel disease and larger-vessel ectasia in a predominantly posterior distribution. We assessed transcranial Doppler (TCD) blood flow velocities in naive and enzyme-treated Fabry patients. TCD...

The authors used proton MRS to investigate neuropathologic correlates in nine patients with proteolipid protein (PLP) gene mutations who did not show cerebral atrophy on cranial MRI. When compared with 16 age-matched control participants, patients with PLP mutations had significant and widespread decreased brain N-acetyl aspartate, a neuronal marke...

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). This enzymatic defect results in the accumulation of the glycosphingolipid globotriaosylceramide (Gb(3); also referred to as ceramidetrihexoside) throughout the body. To investigate the effects of purified alpha-gal A, 1...

The objective of this study is to characterize the brain abnormalities on head MRI of patients with mucolipidosis type IV. Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology. Patients develop corneal clouding, retinal degeneration, spastic quadriparesis, and mental retardation. Patients with this disorder...

This study's purpose was to obtain a quantitative natural history of the cerebrovascular involvement in Fabry disease. Fabry disease is an X-linked recessive disorder due to alpha-galactosidase A deficiency. Progressive accumulation of ceramidetrihexoside within the intima and media of cerebral blood vessels causes ischemic lesions in the majority...

To describe the electroencephalographic findings in mucolipidosis type IV (ML IV), a lysosomal storage disease of unknown etiology characterized clinically by corneal clouding, retinal degeneration and severe psychomotor retardation. Most patients are of Ashkenazi-Jewish ancestry. The EEG findings in this syndrome have not been characterized. We an...

Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities. In an attempt to obtain insight into the nature of the metabolic abnormality in this disorder, we prospectively evaluated 15 consecutive patients, aged 2 to 23 years, over a period of 22 m...

The activator protein for hydrolysis of cerebroside sulfate by arylsulfatase A was purified from pig kidney in high yield. This protein, also known as sphingolipid activator protein-1 and saposin-B, was particularly rich in pig kidney. Purification was achieved by a simple procedure involving homogenation and heat treatment followed by affinity, io...