1214
Book reviews
My favourite chapter was on psychogenic neurological
syndromes. The evaluation of patients with presumed
psychogenic neurological symptoms presents a great challenge to the skills of any physician. Because diseases
affecting the nervous system can manifest in a multitude of
ways, differentiation of true organic from functional neurological manifestations can, at times, be extremely dif®cult.
Psychogenic complaints are frequently embellishments on
true, established organic problems. In this chapter, emphasis
is placed on a mode of examination and a style of practice that
will allow one to gather the information necessary to render
an appropriate diagnosis while at the same time establishing a
trusting therapeutic relationship with the patient. The main
emphasis is placed on the following common psychogenic
symptoms: numbness, weakness, disorders of consciousness,
pseudoseizures and visual complaints.
In conclusion, this book is extremely user-friendly. It is
compact and easy to carry for visits to the intensive care unit
and accident and emergency department. Its greatest use lies
in the fact that it can be used not only as a reference tool for
the practising neurologist, but also as a teaching resource for
general physicians, casualty of®cers, and even medical
students. This book will be an excellent addition to any
neurology ward, library or accident/emergency department.
Savvas Hadjikoutis
University Hospital of Wales,
Cardiff, UK
DOI: 10.1093/brain/awh059
GENETICS OF MITOCHONDRIAL DISEASES
Edited by Ian Holt
2003. Pp. 376. Oxford: Oxford University Press
Price £65. ISBN 0-19-850865-4
Genetics of Mitochondrial Diseases gathers as its authors a
group of renowned international contributors. It is aimed at
everyone with an interest in mitochondrial function and
dysfunction, from basic scientists to registrars seeing patients
with mitochondrial disorders in clinic. It therefore covers
many aspects of mitochondrial disease; indeed, the book
provides even more than the title suggests, covering the
basics of mitochondrial structure and function as well as their
role in disease. This comprehensive treatment is a great
strength of the book and, combined with its readability,
makes it of value to those new to the ®eld; no prior knowledge
is required to obtain valuable information and understanding
from it.
The book is divided into ®ve sections, covering mitochondrial structure and function, the role of mitochondrial DNA
mutations in disease, the involvement of nuclear genes in
mitochondrial disease, the role of mitochondria in neurodegeneration and ageing, and current directions and future
prospects for research in this ®eld.
Downloaded from http://brain.oxfordjournals.org/ by guest on September 30, 2016
huge amount of information. The text is clearly not intended
to be exhaustive, but if more detailed information is required
this can always be found from the references.
The ®rst chapter gives an overview of the fundamental
concepts of neuroanatomy. Neuroanatomy is frequently
considered by trainees to be one of the most technically
intricate disciplines that they must study. This chapter
attempts to review the basic anatomical concepts necessary
to evaluate the historical and physical ®ndings most often
seen with acute neurological problems. As the authors very
rightly comment, mastery of these simple principles and a
fundamental understanding of the overall organization of the
nervous system allows the accurate localization of disease
entities.
The second chapter gives the basic principles of how to
take a carefully selected history and perform physical
examination of a patient with an acute neurological complaint. Very helpful summary tables and algorithms support
the very well written text in this chapter.
The remaining 12 chapters discuss in detail how to evaluate
patients with common neurological complaints: altered states
of consciousness, acute focal neurological de®cits, acute
generalized weakness, movement disorders, headache, acute
blindness, double vision, abnormal pupils, neurological trauma,
psychogenic neurological syndromes, seizures, and neck and
back pain. These chapters are easy to read, with clear and helpful
tables, ®gures and algorithms. The text is extensively referenced
throughout. Consideration is given to how to distinguish the
benign from the serious causes of each complaint and how to
evaluate patients rapidly and ef®ciently.
The chapter on acute focal neurological de®cits describes
useful techniques to localize the anatomical lesion causing
the patient's symptoms. The authors give useful clues to
consider in determining whether a lesion in the brain, the
brainstem, the spinal cord, the peripheral nerves or the
muscles may be the cause of symptoms. This chapter includes
a comprehensive review of acute stroke management
supported by evidence-based medicine.
The evaluation of headache is a common task for any
physician working in the acute care setting. The authors
include a very comprehensive chapter, highly illustrated, on
the evaluation of headache. They aim to help readers to apply
their skills to sorting the benign from the serious causes of
headache. The chapter includes a comprehensive discussion
on the management of subarachnoid haemorrhage. The
authors provide tables with important historical facts to elicit
during the evaluation. They also give a very useful algorithm
regarding laboratory evaluation of patients presenting with
acute headache.
Seizure is frequently the presenting symptom that precipitates the patient's entrance into the medical care system. The
authors provide an informative review on the evaluation and
stabilization of seizures. There are algorithms for the
approach to a patient presenting with the ®rst seizure, and
status epilepticus.
Book reviews
and ageing are the topic of the fourth section. First, ways in
which mitochondrial dysfunction may result in cell death are
discussed, including loss of ATP production, loss of calcium
homeostasis and increased free radical production, along with
the role of the mitochondria in the induction of apoptosis.
This is followed by discussion of how these alterations in
cellular function may result in neurodegenerative disorders in
a chapter that includes the current evidence supporting the
involvement of mitochondria in a number of diseases, such as
Alzheimer's and Parkinson's. The following chapter, dealing
with the mechanism of accumulation of mutations in the
mitochondrial genome throughout age, is written in a more
narrative style then the rest of the book, and as such is
strongly biased to the views of the author. However, this is
clearly stated and I found this chapter fascinating to read.
The ®nal section begins with two chapters discussing ways
in which model systems allow the study of certain aspects of
mitochondrial diseases. First, the use of mammalian cell lines
carrying more than one mitochondrial DNA genotype to
understand the mechanisms of segregation of mitochondrial
DNA is considered. Secondly, there is an account of the use
of mouse models with mutations in nuclear genes encoding
mitochondrial proteins and, more recently, with mutations in
the mitochondrial genome itself. The next chapter deals with
genetic counselling of patients with mitochondrial disorders.
As a scientist with no contact with patients, I found this an
eye-opening chapter about the complexities of dealing with
families suffering from these diseases in the clinic. The ®nal
chapter gives the book a more hopeful conclusion, presenting
the possibilities and challenges for research into future
treatment options using gene therapy.
Overall, I found this to be a very well-written book that is
clearly and logically set out. In a book such as this some
overlap is unavoidable as different mitochondrial diseases or
functions are discussed in the context of each subject.
However, I felt repetition was minimal, serving only to ensure
that each chapter could be read as a separate entity and to
clarify some of the more fundamental points under discussion. In conclusion, I enjoyed reading the book and felt that
my knowledge of mitochondrial disease was broadened in the
process. I would recommend this book to people involved in
any aspect of mitochondrial disease.
Fiona M. Menzies
Neurodegeneration and Aging Unit,
Neurogenetics Branch,
NINDS, NIH,
Bethesda, MD,
USA
DOI: 10.1093/brain/awh093
Downloaded from http://brain.oxfordjournals.org/ by guest on September 30, 2016
Section 1 gives the reader a background for later topics by
offering a thorough description of normal mitochondrial
function. It begins by covering mitochondrial DNA replication and repair, describing the mechanisms and machinery
involved. A description of the mechanism of expression of
genes in the mitochondrial genome follows, including both
the transcription and the translation of the encoded proteins.
Mitochondrial biogenesis and the targeting of proteins to the
mitochondria is the topic of the next section, covering the
signals and machinery required for import of proteins to the
mitochondria and the protease system required for processing
and turnover of these proteins. The ®nal chapter of this
section deals in some detail with the nuances of oxidative
phosphorylation. Whilst not all functions of mitochondria are
covered in this section, other functions are not overlooked
and are dealt with throughout the book as they become
relevant to the mechanisms of disease. An aspect of the book
that increases its value for those with some prior knowledge
of the ®eld is the recurring theme of the correction of longheld dogmas concerning mitochondria. For example, it has
been held that mitochondrial DNA is more sensitive to
mutation due to its lack of repair mechanisms and protective
histones; however, Chapter One discusses evidence to show
that mitochondria do have the ability to repair certain types of
DNA damage, and it is explained that, rather than being
`naked', mitochondrial DNA is actually part of a nucleoprotein complex consisting of a number of copies of mtDNA,
termed `nucloids'.
The second section moves into mitochondrial diseases,
their clinical presentations and the genes involved in them.
The opening chapter discusses the clinical manifestations of
diseases caused by mutations in the mitochondrial genome.
The three chapters following this cover current understanding
of the mechanisms by which mitochondrial DNA mutations
result in these diseases. Each chapter concentrates on one of
the major groups of mutations, rearrangements of mitochondrial DNA, mutations in genes required for mitochondrial
protein synthesis or mutations in genes encoding respiratory
chain subunits; in the case of this last group of genes the focus
is on Leber's hereditary optic neuropathy in more detail as an
example of the diseases in this class. Section 3 continues in a
similar vein, focusing on the role of mutations in the nuclear
genome that result in mitochondrial disorders. Nuclear
mutations resulting in depletion or deletion of mitochondrial
DNA and the mechanisms and consequences of this are
discussed in the ®rst chapter of this section. The second
chapter covers nuclear gene mutations involved either
directly or indirectly in the oxidative phosphorylation pathway.
The effect of mitochondrial dysfunctions on cellular
function and subsequently their role in neurodegeneration
1215